Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1.

ABSTRACT: Nuclear-encoded mitochondrial proteins rely on N-terminal targeting sequences (N-MTS) for their import. Most N-MTSs are cleaved in the matrix by the mitochondrial processing peptidase (MPP), a heterodimeric metalloprotease composed of (α) and catalytic (β) subunits, essential for the maturation of imported proteins. Import and processing of phosphatase and tensin homolog-induced putative kinase 1 (PINK1), a kinase implicated in Parkinson's disease, govern its ability to sense mitochondrial damage. The current paradigm suggests that PINK1 undergoes two sequential processing steps: first, MPP removes the PINK1 N-MTS in the matrix; second, the inner mitochondrial membrane protease PARL cleaves the PINK1 transmembrane domain, leading to PINK1 degradation. Upon depolarization, PINK1 escapes pro

SUBMITTER: Bayne AN 

PROVIDER: S-EPMC12670562 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature