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Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia
- Source :
- iScience, Vol 24, Iss 1, Pp 101972-(2021), iScience
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Summary There is evidence that ATM mutated in ataxia-telangiectasia (A-T) plays a key role in protecting against mitochondrial dysfunction, the mechanism for which remains unresolved. We demonstrate here that ATM-deficient cells are exquisitely sensitive to nutrient deprivation, which can be explained by defective cross talk between the endoplasmic reticulum (ER) and the mitochondrion. Tethering between these two organelles in response to stress was reduced in cells lacking ATM, and consistent with this, Ca2+ release and transfer between ER and mitochondria was reduced dramatically when compared with control cells. The impact of this on mitochondrial function was evident from an increase in oxygen consumption rates and a defect in mitophagy in ATM-deficient cells. Our findings reveal that ER-mitochondrial connectivity through IP3R1-GRP75-VDAC1, to maintain Ca2+ homeostasis, as well as an abnormality in mitochondrial fusion defective in response to nutrient stress, can account for at least part of the mitochondrial dysfunction observed in A-T cells.<br />Graphical Abstract<br />Highlights • Hypersensitivity to glucose deprivation in ATM-deficient cells • Defective ER-mitochondrion cross talk after nutrient stress in these cells • Markedly reduced Ca2+ transfer between these two organelles in ATM-deficient cells • Mitochondrial dysfunction in response to nutrient stress in the absence of ATM<br />Cell Biology; Organizational Aspects of Cell Biology; Functional Aspects of Cell Biology
- Subjects :
- Multidisciplinary
Functional Aspects of Cell Biology
Chemistry
Endoplasmic reticulum
Cell Biology
Mitochondrion
medicine.disease
Organizational Aspects of Cell Biology
Article
Cell biology
mitochondrial fusion
Mitophagy
Organelle
Ataxia-telangiectasia
medicine
lcsh:Q
lcsh:Science
Homeostasis
Function (biology)
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 24
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- iScience
- Accession number :
- edsair.doi.dedup.....6529c7d930f825eb447358a0fa5bd669