Year: 2018
Type: dissertation
Abstract: Mitophagy, the degradation of damaged mitochondria, and mitochondrial biogenesis, the formation of new mitochondria, are two critical mitochondrial quality control pathways that maintain a healthy mitochondrial network and thus a healthy cell. We propose that the mitochondrial protease presenilins-associated rhomboid-like (PARL) coordinates these two processes. PARL undergoes regulated cleavage, termed β cleavage, in response to mitochondrial stress to produce N-terminally cleaved β PARL and a 25 amino acid peptide, Pβ. We have recently demonstrated that β PARL promotes mitochondrial fragmentation and has reduced proteolytic activity for a key component of PINK1/Parkin-mediated mitophagy, PINK1, which may instigate mitophagy. In contrast, Pβ’s putative role and mechanism of action in mitochondrial biogenesis remains poorly defined. In this thesis, I determined that the mitochondrial Pβ peptide translocates to the nucleus where it associates with chromatin. Together, these results further support PARL as a key coordinator of mitophagy and mitochondrial biogenesis.
Source: TSpace (University of Toronto)
Author: Wendy G. Tan
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2908582563