Abstract
BackgroundRab32 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.ResultsTo 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.ConclusionsRab32 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”.
Highlights
Rab32 is a small GTPase associated with multiple organelles but is enriched at the endo‐ plasmic reticulum (ER)
We propose to call this type of selective autophagy “mitochondria-associated membrane (MAM)-phagy”
Rab32 has been detected on lysosomes, where it controls signaling by the mammalian target of rapamycin complex 1 [12]
Summary
Rab is a small GTPase associated with multiple organelles but is enriched at the endo‐ plasmic reticulum (ER). Rab localizes to the cytosol, mitochondria, Golgi, and lysosomerelated organelles (LROs) such as the melanosome and autophagosome [2]. This small GTPase has diverse functions at these organelles, but is abundant on Herrera‐Cruz et al Biol Direct (2021) 16:22. Rab has been detected on lysosomes, where it controls signaling by the mammalian target of rapamycin complex 1 (mTORC1) [12]. Taken together, these studies indicate Rab controls trafficking steps at multiple locations on the secretory pathway
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