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The involvement of organelles in cell death is well established especially for endoplasmic reticulum, lysosomes and mitochondria. However, the role of the peroxisome is not well known, though peroxisomal dysfunction favors a rupture of redox equilibrium. To study the role of peroxisomes in cell death, 158 N murine oligodendrocytes were treated with 7-ketocholesterol (7 KC: 25-50 μM, 24 h). The highest concentration is known to induce oxiapoptophagy (OXIdative stress + APOPTOsis + autoPHAGY), whereas the lowest concentration does not induce cell death. In those conditions (with 7 KC: 50 μM) morphological, topographical and functional peroxisome alterations associated with modifications of the cytoplasmic distribution of mitochondria, with mitochondrial dysfunction (loss of transmembrane mitochondrial potential, decreased level of cardiolipins) and oxidative stress were observed: presence of peroxisomes with abnormal sizes and shapes similar to those observed in Zellweger fibroblasts, lower cellular level of ABCD3, used as a marker of peroxisomal mass, measured by flow cytometry, lower mRNA and protein levels (measured by RT-qPCR and western blotting) of ABCD1 and ABCD3 (two ATP-dependent peroxisomal transporters), and of ACOX1 and MFP2 enzymes, and lower mRNA level of DHAPAT, involved in peroxisomal β-oxidation and plasmalogen synthesis, respectively, and increased levels of very long chain fatty acids (VLCFA: C24:0, C24:1, C26:0 and C26:1, quantified by gas chromatography coupled with mass spectrometry) metabolized by peroxisomal β-oxidation. In the presence of 7 KC (25 μM), slight mitochondrial dysfunction and oxidative stress were found, and no induction of apoptosis was detected; however, modifications of the cytoplasmic distribution of mitochondria and clusters of mitochondria were detected. The peroxisomal alterations observed with 7 KC (25 μM) were similar to those with 7 KC (50 μM). In addition, data obtained by transmission electron microcopy and immunofluorescence microscopy by dual staining with antibodies raised against p62, involved in autophagy, and ABCD3, support that 7 KC (25-50 μM) induces pexophagy. 7 KC (25-50 μM)-induced side effects were attenuated by α-tocopherol but not by α-tocotrienol, whereas the anti-oxidant properties of these molecules determined with the FRAP assay were in the same range. These data provide evidences that 7 KC, at concentrations inducing or not cell death, triggers morphological, topographical and functional peroxisomal alterations associated with minor or major mitochondrial changes., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Since the first report by Rhodin in 1954, our knowledge on mammalian microbodies/peroxisomes has known several periods. An initial two decades period (1954-1973) has contributed to the biochemical individualisation of peroxisomes as a new class of subcellular organelles (de Duve, 1965). The corresponding research period failed to define a clear role of mammalian peroxisomes in vital functions and intermediary metabolism, explaining why feeling that peroxisomes might be in the human cell oddities has prevailed during several decades. The period standing from 1973 to nowadays has progressively removed this cell oddity view of peroxisomes by highlighting vital function and metabolic role of peroxisomes in health and disease along with genetic and metabolic regulation of peroxisomal protein content, organelle envelope formation and protein signal targeting mechanisms. Research on peroxisomes and their response to various drugs and metabolites, dietary and physiological conditions has also played a key role in the discovery of peroxisome proliferator activated receptors (PPARs) belonging to the nuclear hormone receptor superfamily and for which impact in science and medicine goes now by far beyond that of the peroxisomes., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Brown (BAT) and white (WAT) adipose tissues play a key role in the body energy balance orchestrated by the central nervous system. Hibernators have developed a seasonal obesity to respond to inhospitable environment. Jerboa is one of the deep hibernator originated from sub-desert highlands. Thus, this animal represents an excellent model to study cold adaptation mechanism. We report that the adipogenic factor PPARgamma exhibits a differential expression between BAT and WAT at mRNA level. A specific induction was only seen in WAT of pre-hibernating jerboa. Interestingly, PPAR beta/delta is specifically induced in BAT and brain of pre-hibernating jerboa, highlighting for the first time the possible key role of this ubiquitous isoform in the cold adaptation of this true hibernator. Inductions of PPARgamma(2) in WAT and PPAR beta/delta in BAT are blunted by a hypolipemic drug, the ciprofibrate. These changes may be correlated with hibernation arrest and death of treated jerboa. Mitochondrial acyl-CoA dehydrogenase and peroxisomal acyl-CoA oxidase activities in brown and white adipose tissues are decreased up to 85% during cold acclimatization (without food privation). These enzyme activities are subject to a strong induction in BAT and in WAT (3.4-7.5 fold) during the hibernation period. The BAT thermogenesis marker is also largely induced (approximately 4 fold of UCP1 mRNA level) during pre-hibernation period. Unexpectedly, treatment with ciprofibrate deeply affects lipolysis in BAT by increasing acyl-CoA dehydrogenase activity (3.4 fold) and acyl-CoA oxidase at both activity and mRNA levels (2.8 and 3.8 fold, respectively) and enhances strongly UCP1 mRNA level (9.5 fold) during pre-hibernation.

Jerboa (Jaculus orientalis) is a deep hibernator originating from sub-desert highlands and represents an excellent model to help to understand the incidence of seasonal variations of food intake and of body as well as environmental temperatures on lipid metabolism. In jerboa, hibernation processes are characterized by changes in the size of mitochondria, the number of peroxisomes in liver and in the expression of enzymes linked to fatty acid metabolism. In liver and kidney, cold acclimatization shows an opposite effect on the activities of the mitochondrial acyl-CoA dehydrogenase (-50%) and the peroxisomal acyl-CoA oxidase (AOX) (+50%), while in brown and white adipose tissues, both activities are decreased down to 85%. These enzymes activities are subject to a strong induction in brown and in white adipose tissue (3.4- to 7.5-fold, respectively) during the hibernation period which is characterized by a low body temperature (around 10 degrees C) and by starvation. Expression level of AOX mRNA and protein are increased during both pre-hibernation and hibernation periods. Unexpectedly, treatment with ciprofibrate, a hypolipemic agent, deeply affects lipolysis in brown adipose tissue by increasing acyl-CoA dehydrogenase activity (3.4-fold), both AOX activity and mRNA levels (2.8- and 3.8-fold, respectively) during pre-hibernation. Therefore, during pre-hibernation acclimatization, there is a negative regulation of fatty acid degradation allowing to accumulate a lipid stock which is later degraded during the hibernation period (starvation) due to a positive regulation of enzymes providing the required energy for animal survival.