A well-oiled machine: DNM2/dynamin 2 helps keep hepatocyte lipophagy running smoothly

Liver steatosis is characterized by an abnormal buildup of hepatic fat content. Our understanding of how this fat balance is normally regulated remains limited. Recently, autophagy has been implicated as one potential mechanism contributing to the breakdown of cytoplasmic fat storage organelles known as lipid droplets (LDs) in the hepatocyte. In our recent publication, we show that the large GTPase DNM2/dynamin 2 helps promote lipophagic turnover by facilitating the scission of nascent lysosomes from autolysosomal tubules during autophagic flux. Genetic and pharmacological perturbations of DNM2 function in cultured cells result in the generation of aberrantly long autolysosomal reformation tubules. As a consequence, hepatocytes accumulate LDs. An alleviation of DNM2 inhibition results in the scission of reformation tubules and the return of LD turnover to normal levels. DNM2 therefore plays a critical role in the regulation of the lipophagic machinery in the hepatocyte.