Autophagy Regulates Membrane Homeostasis in T Lymphocytes

Autophagy Regulates Membrane Homeostasis in T Lymphocytes Autophagy is a highly conserved intracellular process targeting cytoplasmic components for bulk degradation that has been extensively characterized in Saccharomyces cerevisiae . Recent work from our lab has shown this process to be indispensable for the survival of peripheral T lymphocytes in vivo . In addition to bulk cytoplasmic targeting, autophagy has been proposed to regulate other cellular components including mitochondria and endoplasmic reticulum. In T lymphocytes lacking the essential autophagy protein Atg7, there is an expansion of cytoplasmic membranous structures. These vesicles occupy more than twice the cytoplasmic volume of vesicles in wild type T lymphocytes. Although the massive onset of death is not incurred until after thymic egress, thymocytes lacking Atg7 already have expanded cytoplasmic membranes. A microarray performed on naïve T lymphocytes shows the transcriptional upregulation of many vesicle trafficking and lipid particle formation proteins. Also upregulated are several components of a mitochondrial shuttle pathway for long fatty acid chains, the acyl‐carnitine pathway. Analysis of the acyl‐chain intermediates of this pathway by LC/MS showed an upregulation in the β‐oxidation of several lipids, most notably stearic acid. This pathway has been shown to be upregulated in rat hepatocytes to adjust to high fat diets and skeletal muscles of exercising individuals to maintain healthy mitochodria. These data suggest another function of autophagy in T lymphocytes is to regulate the expansion of vesicles in order to reduce lipid toxicity.