Mitochondria-associated membrane protein PACS2 maintains right cardiac function in hypobaric hypoxia.

ABSTRACT: Hypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but the mechanism was unclear. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were downregulated in HH. Metabolomics analysis indicated suppression of glucose and fatty acids aerobic oxidation in HH conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting mitophagy and energy metabolism in HH. Pacs2 overexpression reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiom

SUBMITTER: Yang J 

PROVIDER: S-EPMC10034453 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature