Depletion of TMEM65 leads to oxidative stress, apoptosis, induction of mitochondrial unfolded protein response, and upregulation of mitochondrial protein import receptor TOMM22.

ABSTRACT: Mutation in the transmembrane protein 65 gene (TMEM65) results in mitochondrial dysfunction and a severe mitochondrial encephalomyopathy phenotype. However, neither the function of TMEM65 nor the cellular responses to its depletion have been fully elucidated. Hence, we knocked down TMEM65 in human cultured cells and analyzed the resulting cellular responses. Depletion of TMEM65 led to a mild increase in ROS generation and upregulation of the mRNA levels of oxidative stress suppressors, such as NFE2L2 and SESN3, indicating that TMEM65 knockdown induced an oxidative stress response. A mild induction of apoptosis was also observed upon depletion of TMEM65. Depletion of TMEM65 upregulated protein levels of the mitochondrial chaperone HSPD1 and mitochondrial protease LONP1, indica

SUBMITTER: Urushima Y 

PROVIDER: S-EPMC7725676 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature