LONP1 Is Required for Maturation of a Subset of Mitochondrial Proteins, and Its Loss Elicits an Integrated Stress Response.

ABSTRACT: LONP1, an AAA+ mitochondrial protease, is implicated in protein quality control, but its precise role in this process remains poorly understood. In this study, we have investigated the role of human LONP1 in mitochondrial proteostasis and gene expression. Depletion of LONP1 resulted in partial loss of mitochondrial DNA (mtDNA) and a complete suppression of mitochondrial translation associated with impaired ribosome biogenesis. The levels of a distinct subset of mitochondrial matrix proteins (SSBP1, MTERFD3, FASTKD2, and CLPX) increased in the presence of a catalytically dead form of LONP1, suggesting that they are bona fide LONP1 substrates. Unexpectedly, the unprocessed forms of the same proteins also accumulated in an insoluble protein fraction. This subset of unprocessed matrix proteins

SUBMITTER: Zurita Rendon O 

PROVIDER: S-EPMC6168981 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature