Figure 1.
The small molecule Torin1 can inhibit the kinase mTOR, resulting in a relief of the mTOR-dependent block of MARCH5 targeting to peroxisomes. MARCH5 is inserted into the peroxisomal membrane in a PEX19- and PEX3-dependent manner. MARCH5 ubiquitinates the abundant peroxisomal membrane protein PMP70 with the help of an unknown ubiquitin (Ub)-conjugating enzyme (E2). The ubiquitinated PMP70 molecules are recognized by ubiquitin-binding autophagy receptors, like NBR1 or p62, that link the organelle to the autophagosome, resulting in the autophagic degradation of the peroxisome via pexophagy.