Mitochondrial hitch-hiking of Pink1 mRNA supports axonal mitophagy

Autophagy. 2022 Dec;18(12):3048-3049. doi: 10.1080/15548627.2022.2070332. Epub 2022 May 3.

Abstract

Mitostasis, the process of mitochondrial maintenance by biogenesis and degradative mechanisms, is challenged by the extreme length of axons. PINK1 (PTEN induced putative kinase 1) is a mitochondrial protein that targets damaged mitochondria for mitophagy. In reconciling the short half-life of PINK1 with the need for mitophagy of damaged axonal mitochondria, we found that axonal mitophagy depends on local translation of the Pink1 mRNA. Using live-cell imaging, we detected co-transport of the Pink1 mRNA on mitochondria in neurons, which is crucial for mitophagy in distal parts of the cell. Here we discuss how the coupling of the transcript of a short-lived mitochondrial protein to the movement of its target organelles contributes to our understanding of mitostasis in neurons.

Keywords: Axonal biology; RNA transport; local translation; mitochondria; mitophagy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology
  • Axons / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • Mitophagy* / genetics
  • Protein Kinases* / genetics
  • Protein Kinases* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • RNA, Messenger
  • Protein Kinases
  • Ubiquitin-Protein Ligases
  • Mitochondrial Proteins