Folliculin–A tumor suppressor at the intersection of metabolic signaling and membrane traffic

Abstract

The Birt-Hoge-Dubé syndrome tumor suppressor Folliculin is a regulator of metabolism and has as a wide range of cellular and organismal phenotypes associated with its disruption. However, the molecular mechanisms which underlie its functions are poorly understood. Folliculin has been described to associate with lysosomes in response to nutrient depletion and form a key part of the signaling network that controls the activity of mTORC1. We recently reported that Folliculin can control the nutrient dependent cytoplasmic distribution of lysosomes by promoting the formation of a complex with the Golgi-associated small GTPase Rab34 and its effector RILP. We thus define a mechanistic connection between the lysosomal nutrient signaling network and the transport machinery that controls the distribution and dynamics of this organelle. Here we summarise the main conclusions from that study, attempt to integrate our findings with other recent studies on lysosome distribution/dynamics, and discuss the potential consequences of the dysregulation of this processes caused by Folliculin loss for Birt-Hoge-Dubé syndrome and normal cell function.