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Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia.

Publication ,  Journal Article
Yeo, AJ; Chong, KL; Gatei, M; Zou, D; Stewart, R; Withey, S; Wolvetang, E; Parton, RG; Brown, AD; Kastan, MB; Coman, D; Lavin, MF
Published in: iScience
January 22, 2021

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.

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

January 22, 2021

Volume

24

Issue

1

Start / End Page

101972

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yeo, A. J., Chong, K. L., Gatei, M., Zou, D., Stewart, R., Withey, S., … Lavin, M. F. (2021). Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia. IScience, 24(1), 101972. https://doi.org/10.1016/j.isci.2020.101972
Yeo, Abrey J., Kok L. Chong, Magtouf Gatei, Dongxiu Zou, Romal Stewart, Sarah Withey, Ernst Wolvetang, et al. “Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia.IScience 24, no. 1 (January 22, 2021): 101972. https://doi.org/10.1016/j.isci.2020.101972.
Yeo AJ, Chong KL, Gatei M, Zou D, Stewart R, Withey S, et al. Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia. iScience. 2021 Jan 22;24(1):101972.
Yeo, Abrey J., et al. “Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia.IScience, vol. 24, no. 1, Jan. 2021, p. 101972. Pubmed, doi:10.1016/j.isci.2020.101972.
Yeo AJ, Chong KL, Gatei M, Zou D, Stewart R, Withey S, Wolvetang E, Parton RG, Brown AD, Kastan MB, Coman D, Lavin MF. Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia. iScience. 2021 Jan 22;24(1):101972.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

January 22, 2021

Volume

24

Issue

1

Start / End Page

101972

Location

United States