mTOR signaling in autophagy regulation in the kidney.
Cells possess adaptive biosynthetic systems to maintain cellular energy levels for survival under adverse environmental conditions. Autophagy is an evolutionarily conserved cellular catabolic process that breaks down and recycles cytosolic material including macromolecules and organelles through lysosomal degradation. This catabolic process, represented by macroautophagy, is induced by a variety of cellular stresses such as nutrient starvation, which causes a shortage of cellular energy for cells to maintain cellular homeostasis and essential biological activities. In contrast, upon nutrient availability, cells stimulate anabolic processes. The mechanistic/mammalian target of rapamycin, a serine/threonine protein kinase, is a key player in stimulating cellular anabolism in response to nutrients and growth factors, and plays a crucial role in suppressing autophagy activity. Growing evidence has suggested that autophagy activity is required for the maintenance and physiological functions of renal cells including proximal tubular cells and podocytes. In this article, we discuss recent progress in the regulation of autophagy by mechanistic/mammalian target of rapamycin signaling.
Life Sciences Institute, Department of Molecular and Integrative Physiology, Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. Electronic address: inokik@umich.edu.
Ken
K
Inoki
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071189:Autophagy-Related Protein-1 Homolog; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007668:Kidney / Q000166:cytology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000071189:Autophagy-Related Protein-1 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C484754:ULK1 protein, human
AMPK; Autophagy; mTOR; mTORC1; podocyte; rapamycin; renal proximal tubular cell