Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins View Full Text


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Article Info

DATE

2021-11-07

AUTHORS

Maria Sol Herrera-Cruz, Megan C. Yap, Nasser Tahbaz, Keelie Phillips, Laurel Thomas, Gary Thomas, Thomas Simmen

ABSTRACT

BACKGROUND: Rab32 is a small GTPase associated with multiple organelles but is particularly enriched at the endoplasmic reticulum (ER). Here, it controls targeting to mitochondria-ER contacts (MERCs), thus influencing composition of the mitochondria-associated membrane (MAM). Moreover, Rab32 regulates mitochondrial membrane dynamics via its effector dynamin-related protein 1 (Drp1). Rab32 has also been reported to induce autophagy, an essential pathway targeting intracellular components for their degradation. However, no autophagy-specific effectors have been identified for Rab32. Similarly, the identity of the intracellular membrane targeted by this small GTPase and the type of autophagy it induces are not known yet. RESULTS: To investigate the target of autophagic degradation mediated by Rab32, we tested a large panel of organellar proteins. We found that a subset of MERC proteins, including the thioredoxin-related transmembrane protein TMX1, are specifically targeted for degradation in a Rab32-dependent manner. We also identified the long isoform of reticulon-3 (RTN3L), a known ER-phagy receptor, as a Rab32 effector. CONCLUSIONS: Rab32 promotes degradation of mitochondrial-proximal ER membranes through autophagy with the help of RTN3L. We propose to call this type of selective autophagy "MAM-phagy". More... »

PAGES

22

References to SciGraph publications

  • 2019-05-30. Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy in NATURE COMMUNICATIONS
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  • 2010-02-26. Ero1α requires oxidizing and normoxic conditions to localize to the mitochondria-associated membrane (MAM) in CELL STRESS AND CHAPERONES
  • 2019-05-03. STX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism in NATURE COMMUNICATIONS
  • 2020-11-11. Inter-organelle membrane contact sites: implications for lipid metabolism in BIOLOGY DIRECT
  • 2013-03-03. Autophagosomes form at ER–mitochondria contact sites in NATURE
  • 2017-01-23. Rab32 connects ER stress to mitochondrial defects in multiple sclerosis in JOURNAL OF NEUROINFLAMMATION
  • 2014-01-17. Regulation of autophagy by the Rab GTPase network in CELL DEATH & DIFFERENTIATION
  • 2009-07-11. A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2017-12-11. RAB37 interacts directly with ATG5 and promotes autophagosome formation via regulating ATG5-12-16 complex assembly in CELL DEATH & DIFFERENTIATION
  • 2019-03-20. Coming together to define membrane contact sites in NATURE COMMUNICATIONS
  • 2008-12-01. Mitofusin 2 tethers endoplasmic reticulum to mitochondria in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13062-021-00311-9

    DOI

    http://dx.doi.org/10.1186/s13062-021-00311-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1142421091

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34743744


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