Lipid transfer at mitochondrial membrane contact sites

Mitochondria are semiautonomous organelles that are actively shaped into an extended reticular network that is not connected to the endomembrane system via vesicular transport. Instead, active lipid exchange occurs between mitochondria and other organelles, such as the endoplasmic reticulum (ER) and lipid droplets (LDs), at mitochondrial membrane contact sites (MCSs), where the two organelles are juxtaposed with each other at a distance of 10–30 nm. Recent advances have led to an increasing understanding of the molecular mechanism that mediates the transfer of different lipid species between these organelles. Here, we highlight advances that demonstrate the role of lipid transfer proteins at ER–mitochondrial and LD–mitochondrial MCSs. Importantly, we summarize the fundamental questions on this topic that remain unanswered.