An anaplerotic approach to correct the mitochondrial dysfunction in ataxia-telangiectasia (A-T).

ABSTRACT:

Background

ATM, the protein defective in the human genetic disorder, ataxia-telangiectasia (A-T) plays a central role in response to DNA double-strand breaks (DSBs) and in protecting the cell against oxidative stress. We showed that A-T cells are hypersensitive to metabolic stress which can be accounted for by a failure to exhibit efficient endoplasmic reticulum (ER)-mitochondrial signalling and Ca2⁺ transfer in response to nutrient deprivation resulting in mitochondrial dysfunction. The objective of the current study is to use an anaplerotic approach using the fatty acid, heptanoate (C7), a metabolic product of the triglyceride, triheptanoin to correct the defect in ER-mitochondrial signalling and enhance cell survival of A-T cells in response to metabolic stress.

Me

SUBMITTER: Yeo AJ 

PROVIDER: S-EPMC8599162 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature