BECN1s, a short splice variant of BECN1, functions in mitophagy

Abstract

Mitochondria selective autophagy, known as mitophagy, plays a pivotal role in several biological processes, such as elimination of the damaged mitochondria, removal of the mitochondria from immature red blood cells and sperm. The defects in mitophagy are associated with a wide spectrum of human diseases, including neurodegenerative disease, aging, cardiac disease and autoimmune disease. However, the mechanism underlying mitophagy remains largely unclear. Here, we report the characterization of a novel splice variant of BECN1/Beclin 1, BECN1s, which is produced by an alternative splicing mechanism. BECN1s is primarily associated with the outer-membrane of mitochondria. Unlike unspliced BECN1, which is essential for nonselective macroautophagy induction, BECN1s is indispensible for mitochondria-selective autophagy. Furthermore, BECN1s plays an important role in starvation- and membrane depolarization-induced mitophagy. Taken together, our findings broaden the view of BECN1 as an important regulator in autophagy, and implicate BECN1s as a specific mitophagy mediator.