Main molecular mechanisms of mitophagy. Mitophagy is regulated by the interaction of mitochondrial proteins with LC3 through different mechanisms. In the PINK1/Parkin pathway, decreased MMP leads to the accumulation of PINK1 to the OMM. PINK1 phosphorylates both ubiquitin and Parkin. Activated Parkin polyubiquitinates specific proteins on the OMM, making available ubiquitins for PINK1 phosphorylation. The ubiquitinated proteins on the OMM allow the interaction of mitochondria with LC3 through specific adaptors, such as p62, Nbr1, OPTN, TAX1BP1, and NDP52. PINK1 can also phosphorylate Mfn2 and promote its ubiquitination by Parkin and rapid degradation, to prevent fusion of damaged mitochondria with healthy organelles. Besides PINK1/Parkin pathway, mitophagy is triggered by the mitochondrial receptors BNIP3, BNIP3L/NIX, FUNDC1, which can bind directly to LC3. Finally, mitochondrial lipids cardiolipin (CL) and C18-ceramide (C18) can move from the mitochondrial cristae to the OMM, where they interact with LC3.