Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome.

ABSTRACT: Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel-Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel-Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHL^R200W mutation, involved in hypoxia-sensing disorders

SUBMITTER: Li S 

PROVIDER: S-EPMC9236906 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature