The He Laboratory

A. Diffused GFP-LC3 signal in wild-type skeletal muscle before exercise

B. GFP-LC3 puncta (autophagosomes) in wild-type skeletal muscle after 80 min of exercise

A. At the start of running (10 m/min)

B. After 95 min of running (18 m/min)

Upper lane: wild-type mouse; lower lane: autophagy-deficient (BCL2 AAA) mouse

Becn2/Beclin 2 is a newly identified Beclin family member that is essential for autophagy. It also regulates lysosomal degradation of endocytosed G protein-coupled receptors (GPCRs), through the N-terminal interaction of Beclin 2 with an adaptor protein GASP1. The cover image illustrates the dual roles of the “cowboy” Beclin 2 (containing an N-terminal domain, CCD (coiled-coil domain) and ECD (evolutionarily conserved domain)): riding the autophagy “horse”, and harnessing the 7-transmembrane GPCR “cow” by the N-terminal “arm” and the GASP1 “lasso”. The background mountain depicts plasma membrane, and cacti and rocks represent various intracellular organelles (including mitochondria, ER and Golgi) and cytosolic proteins. The image is designed by Congcong He, and artwork illustrated by Dorothy Zhu.

Autophagy, an essential lysosomal degradation pathway, plays different roles in distinct metabolic tissues. Hyperactive autophagy benefits insulin-responsive tissues on insulin sensitivity, but reduces pancreatic β cell function by excessive autophagic degradation of insulin-containing vesicles (named vesicophagy). The wave represents an autophagic membrane engulfing insulin granules. The two peaks in the background represent two non-overlapping rheostat curves for autophagy function in insulin-responsive tissues (right) versus in insulin-producing β cells (left), a shift driven by vesicophagy. The image is designed by Kenta Kuramoto and Congcong He, and modified from Ukiyo-e artworks.