PACS-2 functions in colorectal cancer

Kveiborg, Marie; Thomas, Gary

doi:10.18632/aging.101489

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…The physiological function of the MAM, particularly the calcium ux from the ER to the mitochondria and the transport of membrane phospholipids, relies on PACS2 17 . Previous studies have reported the important role of PACS2 in the development and progression of several tumours [18][19][20] . Tumour cells survive in a hypoxic microenvironment because of their in nite proliferation.…”

Section: Introductionmentioning

confidence: 99%

The mitochondria-associated membrane protein PACS2 promotes mitophagy and energy metabolism to maintain right cardiac function in hypobaric hypoxia exposure

Yang

Sun

Chen

et al. 2022

Preprint

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Hypobaric hypoxia (HH) is the primary challenge at high altitude. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxic conditions, but the mechanism remains poorly understood. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were down-regulated in HH conditions. Metabolomics analysis indicated suppression of aerobic oxidation of glucose and fatty acids. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux further inhibiting mitophagy and mitochondrial energy metabolism during HH exposure. Overexpression of Pacs2 reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiomyocyte injury and right cardiac dysfunction induced by HH. Knock-in of Pacs2 recovered HH-induced RV structural and functional impairment. Thus, PACS2 is essential for protecting cardiomyocytes through mechanisms of ER-mitochondria calcium flux, mitophagy, and mitochondrial energy metabolism, thereby maintaining right cardiac function at high altitude.

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Section: Introductionmentioning

confidence: 99%