Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers

Curr Biol. 2008 Jan 22;18(2):102-8. doi: 10.1016/j.cub.2007.12.038.

Abstract

Mitochondria and peroxisomes share a number of common biochemical processes, including the beta oxidation of fatty acids and the scavenging of peroxides. Here, we identify a new outer-membrane mitochondria-anchored protein ligase (MAPL) containing a really interesting new gene (RING)-finger domain. Overexpression of MAPL leads to mitochondrial fragmentation, indicating a regulatory function controlling mitochondrial morphology. In addition, confocal- and electron-microscopy studies of MAPL-YFP led to the observation that MAPL is also incorporated within unique, DRP1-independent, 70-100 nm diameter mitochondria-derived vesicles (MDVs). Importantly, vesicles containing MAPL exclude another outer-membrane marker, TOM20, and vesicles containing TOM20 exclude MAPL, indicating that MDVs selectively incorporate their cargo. We further demonstrate that MAPL-containing vesicles fuse with a subset of peroxisomes, marking the first evidence for a direct relationship between these two functionally related organelles. In contrast, a distinct vesicle population labeled with TOM20 does not fuse with peroxisomes, indicating that the incorporation of specific cargo is a primary determinant of MDV fate. These data are the first to identify MAPL, describe and characterize MDVs, and define a new intracellular transport route between mitochondria and peroxisomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins / metabolism*
  • Peroxisomes / metabolism*
  • RING Finger Domains / physiology
  • Transcription Factors / metabolism*
  • Transport Vesicles / metabolism*
  • Ubiquitin-Protein Ligases

Substances

  • Mitochondrial Proteins
  • Transcription Factors
  • MUL1 protein, human
  • Ubiquitin-Protein Ligases