Peroxisomal-PEX5 Controls Fasting-Induced Lipolysis

Abstract

Lipid droplets (LDs) are dynamic subcellular organelles which play critical roles for lipid homeostasis upon change of nutritional state. Although several organelles such as mitochondria and peroxisomes are involved in lipid metabolism, physiological roles and mediators involved in the spatiotemporal regulation of these subcellular organelles for energy metabolism has largely remained elusive. Our recent study implicates the importance of peroxisomes in the translocation of lipases onto LDs upon fasting cues. Also, we found that peroxisomal protein PEX5 modulates PKA-induced lipolysis by escorting ATGL toward LDs. This is accompanied by KIFC3-mediated migration of peroxisomes, leading to the physical contact between peroxisomes and LDs. In adipocyte-specific PEX5-knockout mice, fasting induced lipolysis is attenuated due to defective ATGL recruitment onto LDs. These results show that PEX5 plays a pivotal role in PKA induced lipolysis that occurs upon nutritional deprivation. We further speculate that the contact between LDs and peroxisomes could facilitate lipid metabolism via exchange of lipid metabolites between the organelles in response to nutritional changes.