Hypoxic Regulation of Mitochondrial Metabolism and Mitophagy in Nucleus Pulposus Cells Is Dependent on HIF-1α-BNIP3 Axis.

ABSTRACT: Nucleus pulposus (NP) cells reside in an avascular and hypoxic microenvironment of the intervertebral disc and are predominantly glycolytic due to robust HIF-1 activity. It is generally thought that NP cells contain few functional mitochondria compared with cells that rely on oxidative metabolism. Consequently, the contribution of mitochondria to NP cell metabolism and the role of hypoxia and HIF-1 in mitochondrial homeostasis is poorly understood. Using mitoQC reporter mice, we show for the first time to our knowledge that NP cell mitochondria undergo age-dependent mitophagy in vivo. Mechanistically, in vitro studies suggest that, under hypoxic conditions, mitochondria in primary NP cells undergo HIF-1α-dependent fragmentation, controlled by modulating the levels of key proteins DRP1 and

SUBMITTER: Madhu V 

PROVIDER: S-EPMC7778522 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature