The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration.

ABSTRACT: Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress.

SUBMITTER: Iqbal MA 

PROVIDER: S-EPMC11258489 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature