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Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.

Chemotherapy and radiotherapy can induce permanent infertility of the treated patient. For prepubertal boys, no option is currently available for the restauration of fertility after anti-cancer treatments. This represents a major concern that moved several centers all over Europe and North America to develop fertility preservation programs that though experimental, are met with high rates of acceptance by the patients and their parents. As no mature gametes can be found in the testicle before puberty, the only available option is the preservation of spermatogonia, diploid germ cells that are precursors of spermatozoa. Retrieval of immature testicular tissue (ITT) through a small biopsy is a safe and efficient method to preserve germ cells before exposure to gonadotoxic treatments. Amongst the several alternatives currently under-study for fertility restoration, transplantation of frozen-thawed ITT fragments is the most promising option. This procedure has not been performed yet on human subjects, although the xeno-transplantation of such fragments to the nude mice provided a valuable model to study. However, every report on human ITT xeno-transplants described an arrest of spermatogenesis at the pachytene spermatocytes stage and an important germ cells loss. After multiple reports of failed attempts at improving the transplantation procedure through in vivo administration of antioxidants or hormonal supplementation and in vitro culture with supporting molecules before grafting, application of tissue engineering led to promising results in autografts of mice testicular tissue. Indeed, administration of nanoparticles delivering Vascular endothelial growth factor (VEGF) and encapsulation in an alginate matrix improved respectively short-term vascularization and spermatogonial survival. The purpose of our project was to obtain a further improvement of testicular tissue transplantation technique applying tissue engineering. In the first part of the experience, we compare, (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

Temperature sensing is involved in many different functions, ranging from fundamental homeostatic regulation to complex inferential processes on outside world properties. Due to the technical difficulty of generating well controlled cooling stimuli, significantly less research has been conducted on cold than on heat perception. The availability of new stimulators, enabling the generation of fast and strong cold stimuli, opens new experimental possibilities. This PhD dissertation aimed to develop new techniques to probe human innocuous cold perception, use these new techniques to probe the neurophysiological mechanisms underlying human cold perception, and assess whether these new techniques could be of interest in a clinical setting. These efforts were directed more specifically in two directions: improving the psychophysical assessment of cold detection and developing stimuli and analysis techniques allowing the exploration of cold evoked activity with electroencephalography., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

Traumatic events are prevalent worldwide and particularly in regions affected by armed conflicts such as the Eastern Democratic Republic of Congo. However, their link with mental and physical health outcomes still needs to be explored. Furthermore, there is a need to identify intrapersonal and interpersonal factors that may influence such relationship. This PhD explored the role of emotion regulation and social support in the occurrence of psychopathological and somatic symptoms in traumatic contexts. Our study populations encompassed three different samples, respectively patients consulting in internal medicine, patients with violence-induced injuries and health workers at frontline in the first wave of the Covid-19 pandemic. Our results showed an association of trauma-related disorders and hypertension with both emotion regulation and social support in the contexts of traumatic events. Our observations point to the necessity to develop interventions in the prevention and treatment of hypertension and trauma related disorders in the aftermath of traumatogenic events, (MED - Sciences médicales) -- UCL, 2022

Diaphanous (DIAPH) three (DIAPH3) is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and, therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and bipolarity of the mitotic spindle. DIAPH3-deficient cells display disorganized cytoskeleton and multipolar spindles. DIAPH3 deficiency disrupts the expression and/or stability of several proteins including the kinetochore-associated protein SPAG5. DIAPH3 and SPAG5 have similar expression patterns in the developing brain and overlapping subcellular localization during mitosis. Knockdown of SPAG5 phenocopies DIAPH3 deficiency, whereas its overexpression rescues the DIAHP3 knockdown phenotype. Conditional inactivation of Diaph3 in mouse cerebral cortex profoundly disrupts neurogenesis, depleting cortical progenitors and neurons, leading to cortical malformation and autistic-like behavior. Our data uncover the uncharacterized functions of DIAPH3 and provide evidence that this protein belongs to a molecular toolbox that links microtubule dynamics during mitosis to aneuploidy, cell death, fate determination defects, and cortical malformation.

Diaphanous (DIAPH) three (DIAPH3) is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and, therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and bipolarity of the mitotic spindle. DIAPH3-deficient cells display disorganized cytoskeleton and multipolar spindles. DIAPH3 deficiency disrupts the expression and/or stability of several proteins including the kinetochore-associated protein SPAG5. DIAPH3 and SPAG5 have similar expression patterns in the developing brain and overlapping subcellular localization during mitosis. Knockdown of SPAG5 phenocopies DIAPH3 deficiency, whereas its overexpression rescues the DIAHP3 knockdown phenotype. Conditional inactivation of in mouse cerebral cortex profoundly disrupts neurogenesis, depleting cortical progenitors and neurons, leading to cortical malformation and autistic-like behavior. Our data uncover the uncharacterized functions of DIAPH3 and provide evidence that this protein belongs to a molecular toolbox that links microtubule dynamics during mitosis to aneuploidy, cell death, fate determination defects, and cortical malformation.

Defects in protein reabsorption by the proximal tubule are toxic for epithelial cells in the nephron and may result in nephropathy. In this study, we showed that the ion channel TRPV4 modulated the endocytosis of albumin and low–molecular weight proteins in the proximal tubule. TRPV4 was found at the basolateral side of proximal tubule cells, and its mechanical activation by cell stretching induced Ca2+ entry into the cytosol, which promoted endocytosis. Trpv4−/− mice presented with mild proximal tubule dysfunction under basal conditions. To challenge endocytic function, the permeability of the glomerular filter was altered by systemic delivery of angiotensin II. The proteinuria induced by this treatment was more severe in Trpv4−/− than in Trpv4+/+ mice. Injecting antibodies against the glomerular basement membrane to induce glomerulonephritis is a more pathophysiologically relevant method of impairing glomerular filter permeability. Albuminuria was more severe in mice that lacked TRPV4 specifically in the proximal tubule than in control mice. These results emphasize the importance of TRPV4 in sensing pressure in the proximal tubule in response to variations in the amount of ultrafiltrate and unveil a mechanism that controls protein reabsorption.

The authors wish to make the following corrections to this paper [...].

Cisplatin (CDDP) is one of the principal chemotherapeutic agents used for the first-line treatment of many malignancies, including non-small cell lung carcinoma (NSCLC). Despite its use for over 40 years, its mechanism of action is not yet fully understood. Store-operated calcium entry (SOCE), the main pathway allowing Ca entry in non-excitable cells, is involved in tumorogenesis, cancer progression and chemoresistance. It has become an attractive target in cancer treatment. In this study, we showed that siRNA-mediated depletion of stromal interaction molecule 1 (STIM1) and transient receptor potential channel 1 (TRPC1), two players of the store-operated calcium entry, dramatically reduced CDDP cytotoxicity in NSCLC cells. This was associated with an inhibition of the DNA damage response (DDR) triggered by CDDP. Moreover, STIM1 depletion also reduced CDDP-dependent oxidative stress. In parallel, SOCE activation induced Ca entry into the mitochondria, a major source of reactive oxygen species (ROS) within the cell. This effect was highly decreased in STIM1-depleted cells. We then conclude that mitochondrial Ca peak associated to the SOCE contributes to CDDP-induced ROS production, DDR and subsequent apoptosis. To the best of our knowledge, this is the first time that it is shown that Ca signalling constitutes an initial step in CDDP-induced apoptosis.

SOCE (Store-Operated Calcium Entry) is the main mechanism by which external Ca enters into non-excitable cells after endoplasmic reticulum emptying. It is implicated in several processes such as proliferation and migration. Alterations in SOCE could initiate or support the development of hallmarks of cancer. In this project, we showed that disruption of the EGFR/ErbB2-dependent signalling by lapatinib and CP-724714, two inhibitors of the receptor tyrosine kinase (RTK), dramatically reduced the amplitude of the SOCE in breast cancer cells. LY294002 and MK2206, two inhibitors of the PI3K/Akt pathway, mimicked the effect of the inhibition of EGFR/ErbB2. In contrast, inhibitors of the MAPK pathway had no effect on SOCE. The involvement of EGFR/ErbB2 receptors and the PI3K/Akt pathway in the regulation of SOCE was confirmed in other cell lines derived from various cancer types. All these results showed that SOCE is positively regulated by the PI3K/Akt pathway and that this effect may be suppressed by the inhibition of the upstream RTKs. Inhibition of SOCE might therefore contribute to the anticancer effects of RTK inhibitors.

Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms. TRPC1/4/5 complexes have recently been involved in the efficiency of synaptic transmission in the hippocampus. We therefore used a mouse model devoid of TRPC1 expression to investigate the involvement of mGluR5-TRPC1 pathway in synaptic plasticity and memory formation. mice showed alterations in spatial working memory and fear conditioning. Activation of mGluR increased synaptic excitability in neurons from WT but not from mice. LTP triggered by a theta burst could not maintain over time in brain slices from mice. mGluR-induced LTD was also impaired in these mice. Finally, acute inhibition of TRPC1 by Pico145 on isolated neurons or on brain slices mimicked the genetic depletion of and inhibited mGluR-induced entry of cations and subsequent effects on synaptic plasticity, excluding developmental or compensatory mechanisms in mice. In summary, our results indicate that TRPC1 plays a role in synaptic plasticity and spatial working memory processes.

Mitochondrial membrane permeabilisation (MMP) is classically considered as a point of no return in several forms of cell death and is involved in numerous diseases such as cancer, neurodegenerative disorders or ischemia/reperfusion injuries. Many studies established that reactive oxygen species (ROS) and Ca(2+) were the prominent inducers of MMP. However, the mechanisms connecting ROS and Ca(2+) to the players of MMP are still a matter of debate.

TRP channels are involved in the control of a broad range of cellular functions such as cell proliferation and motility. We investigated the gating mechanism of TRPC1 channel and its role in U251 glioblastoma cells migration in response to chemotaxis by platelet-derived growth factor (PDGF). PDGF induced an influx of Ca(2+) that was partially inhibited after pretreatment of the cells with SKI-II, a specific inhibitor of sphingosine kinase producing sphingosine-1-P (S1P). S1P by itself also induced an entry of Ca(2+). Interestingly, PDGF- and S1P-induced entries of Ca(2+) were lost in siRNA-TRPC1 treated cells. PDGF-induced chemotaxis of U251 cells was dramatically inhibited in cells treated with SKI-II. This effect was almost completely rescued by addition of synthetic S1P. Chemotaxis was also completely lost in siRNA-TRPC1 treated cells and interestingly, the rescue of migration of cells treated with SKI-II by S1P was dependent on the expression of TRPC1. Immunocytochemistry revealed that, in response to PDGF, TRPC1 translocated from inside of the cell to the front of migration (lamellipodes). This effect seemed PI3K dependent as it was inhibited by cell pre-treatment with LY294002, a PI3-kinase inhibitor. Our results thus identify S1P as a potential activator of TRPC1, a channel involved in cell orientation during chemotaxis by PDGF.

Reference treatment of advanced prostate cancer (PCa) relies on pharmacological or surgical androgen deprivation therapy. However, it is only temporarily efficient as tumor cells inevitably adapt to the low testosterone environment and become hormone-refractory (HRPCa). We observed that androgen removal in HRPCa-derived LNCaP cells causes different alterations in their Ca(2+) homeostasis among which a reduction of ER Ca(2+) content. We show that the decrease in [Ca(2+)]ER is due to a modest overexpression of type 1 IP3R and a threefold increased phosphorylation of IP3R1 on Ser-1716, a protein kinase A (PKA) consensus site, both implicated in ER Ca(2+) leak. Accordingly, ER Ca(2+) content was restored by siRNA-mediated down-regulation of IP3R1 or by inhibition of its phosphorylation by competition with a permeant TAT-peptide containing the Ser-1716 consensus phosphorylation sequence or by treatment with the PKA inhibitor H89. Moreover, inhibition of the IP3R1 phosphorylation by both methods sensitized the LNCaP cells to androgen deprivation-induced apoptosis. In addition, SERCA2b overexpression precluded the effect of androgen deprivation on ER Ca(2+) store content and reduced resistance to androgen deprivation. Taken together, these results indicate that lowering the ER Ca(2+)-store content by increasing IP3R1 levels and IP3R1 phosphorylation by PKA is a protective mechanism by which HRPCa-derived cells escape cell death in the absence of androgenic stimulation.

Prostate cancer (PCa) is the most frequent cancer in men above the age of 50 years. Despite radical prostatectomy or radiation therapy as primary treatment, 15-30% of patients will develop an advanced or metastatic cancer requiring systemic therapies. Reference treatment of advanced PCa relies on pharmacological or surgical androgen deprivation therapy. However, despite initial efficacy of androgen deprivation (AD), the tumor inevitably adapts to low testosterone environment and becomes hormone refractory (HRPCa). A better understanding of the mechanisms of androgen independence is necessary to improve the management of HRPCa. Although autophagy confers chemoresistance in some cancers, its role in the development of HRPCa remained unknown. We found that AD or treatment with the anti-androgen bicalutamide promoted autophagy in HRPCa-derived LNCaP cells. This effect was associated with an inhibition of the PI3K/Akt/mTOR pathway and with a disruption of the complex formed by androgen receptor and the regulatory subunit of PI3K p85. Moreover, genetic or pharmacological inhibition of autophagy restored AD-dependent cell death indicating that autophagy is a protective mechanism against AD in HRPCa cells. Besides, in these same cells, we also observed different modifications of Ca2+ homeostasis after androgen withdrawal among which a reduction of the ER Ca2+ content. We discovered that the [Ca2+]ER decrease was due to the presence of IP3R1 made leakier by their phosphorylation by PKA inhibitor H89 or permeant TAT-peptide containing the Ser-1716 consensus phosphorylation sequence sensitized LNCaP cells to AD, suggesting that [Ca2+]ER can control HRPCa cells resistance to AD. Therefore, we identified two distinct mechanisms by which HRPCa-derived cells manage to overcome cell death that they face in the absence of androgenic stimulation. We hope that these findings will help to device new therapeutic strategies to circumvent hormone independence of advanced PCa., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2015

Richement illustré et particulièrement pédagogique, cet ouvrage, un classique du domaine, accompagné de ses compléments en ligne est la référence en neurosciences pour tout étudiant en psychologie et sciences cognitives, médecine et biologie.

Intrinsic and acquired chemoresistance are frequent causes of cancer eradication failure. Thus, long-term cis-diaminedichloroplatine(II) (CDDP) or cisplatin treatment is known to promote tumor cell resistance to apoptosis induction via multiple mechanisms involving gene expression modulation of oncogenes, tumor suppressors and blockade of pro-apoptotic mitochondrial membrane permeabilization. Here, we demonstrate that CDDP-resistant non-small lung cancer cells undergo profound remodeling of their endoplasmic reticulum (ER) proteome (>80 proteins identified by proteomics) and exhibit a dramatic overexpression of two protein disulfide isomerases, PDIA4 and PDIA6, without any alteration in ER-cytosol Ca(2+) fluxes. Using pharmacological and genetic inhibition, we show that inactivation of both proteins directly stimulates CDDP-induced cell death by different cellular signaling pathways. PDIA4 inactivation restores a classical mitochondrial apoptosis pathway, while knockdown of PDIA6 favors a non-canonical cell death pathway sharing some necroptosis features. Overexpression of both proteins has also been found in lung adenocarcinoma patients, suggesting a clinical importance of these proteins in chemoresistance.

BACKGROUND: Treatment of advanced prostate cancer (PCa) relies on pharmacological or surgical androgen deprivation. However, it is only temporarily efficient. After a few months or years, the tumor relapses despite the absence of androgenic stimulation: a state referred to as hormone-refractory prostate cancer (HRPCa). Although autophagy confers chemoresistance in some cancers, its role in the development of HRPCa remains unknown. METHODS: Autophagic flux was assayed by GFP-LC3 clustering, by LC3-I to LC3-II conversion and transmission electron microscopy. Cell death was detected by sub-G1 quantification and concomitant measurement of transmembrane mitochondrial potential and plasma membrane permeabilization. Inhibition of autophagy was achieved by siRNAs and pharmacological inhibitors. RESULTS: Androgen deprivation or treatment with the anti-androgen bicalutamide promoted autophagy in HRPCa-derived LNCaP cells. This effect was dramatically reduced after depletion of Atg5 and Beclin-1, two canonical autophagy genes, and was associated with an inhibition of the androgen-induced mTOR pathway. The depletion of Atg5 and Beclin-1 significantly increased the level of cell death induced by androgen deprivation or bicalutamide. Finally, the safe anti-malarial drug chloroquine, an inhibitor of autophagy, dramatically increased cell death after androgen deprivation or bicalutamide treatment. CONCLUSION: Taken together, our data suggest that autophagy is a protective mechanism against androgen deprivation in HRPCa cells and that chloroquine could restore hormone dependence. This set of data could lead to the development of new therapeutic strategy against HRPCa. Prostate © 2013 Wiley Periodicals, Inc.

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

TRP channels have been associated with cell proliferation and aggressiveness in several cancers. In particular, TRPC1 regulates cell proliferation and motility, two processes underlying cancer progression. We and others have described the mechanisms of TRPC1-dependent cell migration. However, the involvement of TRPC1 in cell proliferation remains unexplained. In this study, we show that siRNA-mediated TRPC1 depletion in non small cell lung carcinoma cell lines induced G(0)/G(1) cell cycle arrest resulting in dramatic decrease in cell growth. The expression of cyclins D1 and D3 was reduced after TRPC1 knockdown, pointing out the role of TRPC1 in G(1)/S transition. This was associated with a decreased phosphorylation and activation of EGFR and with a subsequent disruption of PI3K/Akt and MAPK downstream pathways. Stimulation of EGFR by its natural ligand, EGF, induced Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry through TRPC1. Ca(2+) entry through TRPC1 conversely activated EGFR, suggesting that TRPC1 is a component of a Ca(2+)-dependent amplification of EGF-dependent cell proliferation.

Sleeping sickness is an infectious disease affecting humans in sub-Saharan Africa. It is caused by the protist Trypanosoma brucei which is transmitted by blood-feeding tsetse flies. This parasite possesses many unique features, including the organisation of the major part of the glycolytic pathway in peroxisome-like organelles known as glycosomes. This compartmentalisation has been shown to be essential for the viability of the parasite. During its life cycle, T. brucei proceeds through several stages. In its mammalian host, the parasite presents itself as a bloodstream form that, for its ATP supply, is dependent on glucose from the host’s blood and in the tsetse fly’s midgut it occurs as the procyclic form. In this latter stage the parasite prefers the less available glucose, but can also feed, for its energy, on amino acids such as proline and glutamine. The enzyme composition of glycosomes from each of these two stages is associated to the parasite’s metabolic needs. Bloodstream trypanosomes have 90% of the glycosomal enzyme content dedicated to glycolysis, while in glycosomes from procyclic cells this number drops to 40-50%, and the parasites develop a more diversified metabolism. Experiments performed in our laboratory have shown an increase in colocalisation of markers for glycosomes and the lysosome during the steps by which trypanosomes differentiate from the bloodstream to the procyclic form. This indicates that autophagy plays a role in the metabolic adaptation of the parasites during differentiation. It has been shown in yeast cells that peroxisomes reach a certain stage where they are no longer able to import matrix proteins from the cytosol. These organelles then, can be considered unable to adapt their enzyme content to changes in carbon source. We propose that a similar situation may happen in T. brucei where mature glycosomes that are rich in glycolytic enzymes and no longer able to import matrix proteins will be specifically degraded when the parasi, La maladie du sommeil est une maladie infectieuse qui affecte l’homme en Afrique subsaharienne. Elle est causée par le protiste Trypanosoma brucei qui est transmis par la mouche tsé-tsé lors d’un repas sanguin. Ce parasite possède de nombreuses caractéristiques uniques, y compris l’organisation d’une grande partie de sa voie glycolytique dans des organites de la famille des peroxisomes, appelées glycosomes. Il a été démontré que cette compartimentation est essentielle pour la viabilité du parasite. Au cours de son cycle de vie, T. brucei passe par plusieurs stades. Chez l’hôte mammifère, il est sous la forme sanguicole qui, pour son approvisionnement en ATP, est dépendante du glucose présent dans le sang de l’hôte. Dans l’intestin de la mouche tsé-tsé, il est présent sous la forme procyclique. A ce stade, le parasite préfère le glucose même s’il est peu disponible, mais peut également utiliser, pour produire son énergie, des acides aminés comme la proline et la glutamine. La composition enzymatique des glycosomes dans ces deux stades est liée aux besoins énergétiques du parasite. Dans la forme sanguicole des trypanosomes, 90% du contenu enzymatique est dédié à la glycolyse ; tandis que dans les glycosomes des cellules procycliques, cette proportion tombe à 40-50% et le parasite développe un métabolisme plus diversifié. Des expériences réalisées dans notre laboratoire ont montré une augmentation de la co-localisation des marqueurs des glycosomes et des lysosomes durant les étapes de différenciation de la forme sanguicole à la forme procyclique. Ceci indique que l’autophagie joue un rôle dans l’adaptation métabolique de ces parasites durant la différenciation. Dans les cellules de levure, il a été montré que les peroxysomes atteignent un certain stade au delà duquel ils ne sont plus capables d’importer des protéines matricielles en provenance du cytosol. Ces organites peuvent alors être considérées comme incapables d’adapter leur contenu enzymatique aux changements de, (FARM 3) -- UCL, 2012