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Autophagy Function and Regulation in Kidney Disease

Renal Section, Central Arkansas Veterans Healthcare System Little Rock, Arkansas and Division of Nephrology, 4300 W 7th St, Little Rock, AR 72205, USA
Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205, USA
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 100;
Received: 27 November 2019 / Revised: 16 December 2019 / Accepted: 19 December 2019 / Published: 7 January 2020
(This article belongs to the Special Issue Molecular Mechanisms of Kidney Injury and Repair)
Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches. View Full-Text
Keywords: autophagy; acute kidney injury; chronic kidney disease; diabetic nephropathy; mTORC1; AMPK; renal fibrosis; apoptosis; regulated necrosis autophagy; acute kidney injury; chronic kidney disease; diabetic nephropathy; mTORC1; AMPK; renal fibrosis; apoptosis; regulated necrosis
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Kaushal, G.P.; Chandrashekar, K.; Juncos, L.A.; Shah, S.V. Autophagy Function and Regulation in Kidney Disease. Biomolecules 2020, 10, 100.

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