Trans-membrane-domain switching controls PINK1 import and fate in mitochondria

ABSTRACT: Mitochondrial targeting of the PINK1 kinase results, under normal conditions, in membrane-potential-driven inner-membrane penetration and cleavage by the resident protease PARL before retrotranslocation and proteasomal degradation. In compromised mitochondria, with reduced membrane potential, inner-membrane incorporation is not achieved, which leads to surface activation of the full-length protein, Parkin recruitment and mitophagy. Here we identify a third pathway in which PINK1 is imported into the mitochondrial matrix. Structural modelling predicts that PINK1's trans-membrane-domain (TMD) is conformationally plastic, forming either an α-helix or α/β-hybrid at the interface between Tim17 of the TIM23-complex for engagement of either ROMO1 or PARL. These mutually exclusive assemblies defin

SUBMITTER: James, S Lorriman 

PROVIDER: S-SCDT-10_1038-S44318-026-00789-X | biostudies-other |

REPOSITORIES: biostudies-other