Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes

Abstract

Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1alpha and the common use of fission machinery, including DRP1, Mff, and hFis1. We have previously shown that MDVs are formed independently of the known mitochondrial fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase). Here, we demonstrate that the retromer complex, a known component of vesicle transport from the endosome to the Golgi apparatus, regulates the transport of MAPL from mitochondria to peroxisomes. An unbiased screen shows that Vps35 and Vps26 are found in complex with MAPL, and confocal imaging reveals Vps35 recruitment to mitochondrial vesicles. Silencing of Vps35 or Vps26A leads to a significant reduction in the delivery of MAPL to peroxisomes, placing the retromer within a novel intracellular trafficking route and providing insight into the formation of MAPL-positive MDVs.

Selective escape of proteins from the mitochondria during mitophagy

“…However, the effects of nocodazole treatment in the present study indicate that microtubule polymerization is required for the translocation of FKBP38 from the mitochondria to the ER. Vesicle transport occurs between various organelles, with such communication having recently been shown to take place between the mitochondria and both peroxisomes and lysosomes 46,47 . Small vesicles might thus be generated as a consequence of mitochondrial membrane damage and then be transported to the ER by the microtubule-dependent trafficking system.…”

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

“…The D620N PD-related mutation in VPS35 displays a dominant negative missorting phenotype of retrograde transport of proteins dependent on the WASH complex [218,222]. WT VPS35 regulates mitochondrial-anchored protein ligase transport from the mitochondria to the peroxisomes [223], suggesting that VPS35 mutations may produce mitochondrial defects in patients. VPS35 is also responsible for divalent metal transporter 1 transport [224].…”

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

“…[33][34][35][36] Recently an export system that transfers proteins from mitochondria to peroxisomes via vesicular trafficking has also been identified. 37 These dynamic properties of mitochondria mean that the mitochondrial proteome is not static, but varies with cell type and state.…”