bims-tofagi 2024-11-03 papers

Free Radic Biol Med. 2024 Oct 29. pii: S0891-5849(24)01014-1. [Epub ahead of print]

Pink1-Dependent Mitophagy in Vascular Smooth Muscle Cells: Implications for Arterial Constriction.

Dongliang Li, Shi Zhang, Jingqi Nie, Shengmiao Yu, Yang Li, Feifei Zheng, Shipeng Bo, Nan Wang, Yanqiu Zhang.

Hypertension is a major global health issue, contributing to significant cardiovascular morbidity and mortality. Mitochondrial dysfunction, particularly through dysregulated mitophagy, has been implicated in the pathogenesis of hypertension. We wanted to find out the relationship between mitochondrial autophagy and changes in arterial smooth muscle cell tension and the molecular mechanism. Using RNA-seq analysis, we identified significant upregulation of autophagy-related genes, including Pink1, in the aortas of spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. Further in vivo and in vitro studies revealed enhanced mitophagy, characterized by increased expression of Pink1 protein. Our experiments showed that knockdown of Pink1 expression by shRNA attenuated KPSS-induced vascular smooth muscle cells (VSMCs) contraction, suggesting that excessive mitophagy contributes to vascular dysfunction in hypertension. These findings highlight Pink1-mediated mitophagy as a crucial player in hypertensive vascular remodeling and present a potential therapeutic target for managing hypertension.

Keywords: Mitophagy; Pink1; arterial constriction; hypertension; smooth muscle cell

DOI: https://doi.org/10.1016/j.freeradbiomed.2024.10.306

Nat Commun. 2024 Oct 29. 15(1): 9347

AAA+ ATPase chaperone p97/VCPFAF2 governs basal pexophagy.

Fumika Koyano, Koji Yamano, Tomoyuki Hoshina, Hidetaka Kosako, Yukio Fujiki, Keiji Tanaka, Noriyuki Matsuda.

Peroxisomes are organelles that are central to lipid metabolism and chemical detoxification. Despite advances in our understanding of peroxisome biogenesis, the mechanisms maintaining peroxisomal membrane proteins remain to be fully elucidated. We show here that mammalian FAF2/UBXD8, a membrane-associated cofactor of p97/VCP, maintains peroxisomal homeostasis by modulating the turnover of peroxisomal membrane proteins such as PMP70. In FAF2-deficient cells, PMP70 accumulation recruits the autophagy adaptor OPTN (Optineurin) to peroxisomes and promotes their autophagic clearance (pexophagy). Pexophagy is also induced by p97/VCP inhibition. FAF2 functions together with p97/VCP to negatively regulate pexophagy rather than as a factor for peroxisome biogenesis. Our results strongly suggest that p97/VCPFAF2-mediated extraction of ubiquitylated peroxisomal membrane proteins (e.g., PMP70) prevents peroxisomes from inducing nonessential autophagy under steady state conditions. These findings provide insight into molecular mechanisms underlying the regulation of peroxisomal integrity by p97/VCP and its associated cofactors.

DOI: https://doi.org/10.1038/s41467-024-53558-x

Blood Adv. 2024 Oct 29. pii: bloodadvances.2024013890. [Epub ahead of print]

The E3 ubiquitin ligase MARCH5 promotes mitochondrial fusion and cell cycle progression in acute myeloid leukemia.

Clement Larrue, Sarah Mouche, Jérôme Tamburini.

DOI: https://doi.org/10.1182/bloodadvances.2024013890