Characterizing the role of the Pbeta peptide: A potential mitochondria to nuclear signal in Mitochondrial quality control
Year: 2016
Type: dissertation
Abstract: The PINK1/Parkin mediated mitophagy pathway is fundamental for maintaining a healthy mitochondrial network. We have previously shown that the mitochondrial rhomboid protease PARL is required for recruitment of Parkin to damaged mitochondria. Self-regulated proteolysis of PARL at its N-terminus, known as β cleavage results in a 25 amino acid peptide (Pβ) and β -PARL. β-cleavage might be required for efficient PINK1/Parkin mediated mitophagy. Based on previous studies on PARL and β-cleavage, we hypothesize that the Pβ-peptide, generated inside mitochondria after PARL senses mitochondrial damage, accumulates in the nucleus and plays a role in mitochondrial-nuclear communication. Using the neuroblastoma cell line SH-SY5Y, we have identified the endogenous Pβ peptide. We demonstrate that upon mitochondrial damage the Pβ peptide generated inside the mitochondria accumulates in the nucleus. Our data suggests that PARL may execute a novel mitochondria-to-nucleus signaling pathway through regulated proteolysis of its N terminus and release of the Pβ peptide.
Source: TSpace (University of Toronto)
Author: Navdeep Deol
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2725675746