**1. Introduction**

There are many functional proteins on the mitochondrial outer membrane. Not only mitochondrial quality control, but also various types of signal transduction including in the innate immune response, is performed on mitochondria as a sca ffold. Mitochondria are dynamic organelles that form diverse networks through morphological changes via their fusion and fission, their intracellular movement along microtubules, and their interaction with other organelles. Since mitochondrial function is tightly regulated by mitochondrial dynamics, its molecular mechanisms and their association with disease have attracted substantial attention. In the ubiquitylation system, E3 ubiquitin ligases play a key role in determining substrate specificity and catalyzing the transfer of ubiquitin from E2 enzymes to the substrate. Growing evidence has shown that E3 ubiquitin ligases are involved in the regulation of mitochondrial functions. HECT domain type E3 ligases have one more transthiolation reaction to transfer the ubiquitin onto the E3, whereas the much more common RING finger domain type ligases transfer ubiquitin directly from E2 to the substrate. MITOL (mitochondrial ubiquitin ligase: also known as MARCH5) is a mitochondrial membrane-associated RING finger E3 ubiquitin ligase and was initially identified as a regulator of mitochondrial dynamics, which involves two di fferent aspects: the regulation of protein activation by K63 ubiquitin chain attachment and the regulation of proteasome-dependent degradation by K48 ubiquitin chain attachment via ubiquitin signaling on the outer mitochondrial membrane. A number of MITOL substrates have been identified so far and their association with disease has been suggested. In this review, we present the latest findings on MITOL as a potential drug target and its relevance to disease and aging.

### **2. Mitochondria and Intracellular Quality Control by MITOL**
