Autophagy in kidney homeostasis and disease.
TLDR
The authors summarize the basics of autophagy and the signalling pathways involved in its regulation, and examine the multiple roles of autophile in kidney cells, from its involvement in kidney maintenance and responses to injury, to its potential contribution to glomerular and tubulointerstitial disease.Abstract:
Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic components. Basal autophagy in kidney cells is essential for the maintenance of kidney homeostasis, structure and function. Under stress conditions, autophagy is altered as part of the adaptive response of kidney cells, in a process that is tightly regulated by signalling pathways that can modulate the cellular autophagic flux — mammalian target of rapamycin, AMP-activated protein kinase and sirtuins are key regulators of autophagy. Dysregulated autophagy contributes to the pathogenesis of acute kidney injury, to incomplete kidney repair after acute kidney injury and to chronic kidney disease of varied aetiologies, including diabetic kidney disease, focal segmental glomerulosclerosis and polycystic kidney disease. Autophagy also has a role in kidney ageing. However, questions remain about whether autophagy has a protective or a pathological role in kidney fibrosis, and about the precise mechanisms and signalling pathways underlying the autophagy response in different types of kidney cells and across the spectrum of kidney diseases. Further research is needed to gain insights into the regulation of autophagy in the kidneys and to enable the discovery of pathway-specific and kidney-selective therapies for kidney diseases and anti-ageing strategies. In this Review, the authors summarize the basics of autophagy and the signalling pathways involved in its regulation, and examine the multiple roles of autophagy in kidney cells, from its involvement in kidney maintenance and responses to injury, to its potential contribution to glomerular and tubulointerstitial disease.read more
Citations
More filters
Journal ArticleDOI
Autophagy in major human diseases
Daniel J. Klionsky,Giulia Petroni,Ravi K. Amaravadi,Eric H. Baehrecke,Andrea Ballabio,Andrea Ballabio,Patricia Boya,José Manuel Bravo-San Pedro,Ken Cadwell,Francesco Cecconi,Francesco Cecconi,Augustine M.K. Choi,Augustine M.K. Choi,Mary E. Choi,Mary E. Choi,Charleen T. Chu,Patrice Codogno,Patrice Codogno,María Isabel Colombo,Ana Maria Cuervo,Vojo Deretic,Ivan Dikic,Zvulun Elazar,Eeva-Liisa Eskelinen,Gian Maria Fimia,David A. Gewirtz,Douglas R. Green,Malene Hansen,Marja Jäättelä,Terje Johansen,Gábor Juhász,Vassiliki Karantza,Claudine Kraft,Guido Kroemer,Nicholas T. Ktistakis,Sharad Kumar,Sharad Kumar,Carlos López-Otín,Kay F. Macleod,Frank Madeo,Jennifer Martinez,Alicia Meléndez,Alicia Meléndez,Noboru Mizushima,Christian Münz,Josef M. Penninger,Josef M. Penninger,Rushika M. Perera,Mauro Piacentini,Mauro Piacentini,Fulvio Reggiori,David C. Rubinsztein,Kevin M. Ryan,Junichi Sadoshima,Laura Santambrogio,Luca Scorrano,Hans-Uwe Simon,Hans-Uwe Simon,Anna Katharina Simon,Anne Simonsen,Anne Simonsen,Alexandra Stolz,Nektarios Tavernarakis,Nektarios Tavernarakis,Sharon A. Tooze,Tamotsu Yoshimori,Junying Yuan,Junying Yuan,Zhenyu Yue,Qing Zhong,Lorenzo Galluzzi,Federico Pietrocola +71 more
TL;DR: In this paper, preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury
Chengyuan Tang,Hailong Han,Mingjuan Yan,Shiyao Zhu,Jing Liu,Zhiwen Liu,Liyu He,Jieqiong Tan,Yu Liu,Hong Liu,Lin Sun,Shao-Bin Duan,Youming Peng,Fuyou Liu,Xiao Ming Yin,Zhuohua Zhang,Zheng Dong +16 more
TL;DR: In this article, Pink1 and Park2 deficiency enhances mitochondrial damage, reactive oxygen species production, and inflammatory response, supporting a critical role of the PINK1-PARK2 pathway in tubular cell mitophagy.
Journal ArticleDOI
The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury
Ying Wang,Jiefu Zhu,Zhiwen Liu,Shaoqun Shu,Ying Fu,Yuxue Liu,Juan Cai,Chengyuan Tang,Yu Liu,Xiaoming Yin,Zheng Dong +10 more
TL;DR: The induction of mitophagy is demonstrated in mouse models of septic AKI induced by lipopolysaccharide treatment or by cecal ligation and puncture and it is suggested that the PINK1/PARK2 pathway ofMitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function in sepsis.
Journal ArticleDOI
Mitochondria ROS and mitophagy in acute kidney injury
TL;DR: Recent advances are reviewed in the understanding of the relationship between ROS and mitophagy, the differentMitophagy pathways, the relationships between mitophile and cell death, and the relevance of these processes in the pathogenesis of AKI are reviewed.
Journal ArticleDOI
AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury.
TL;DR: In this paper, both mTOR and AMPK have been implicated in the regulation of autophagy in cisplatin-induced acute kidney injury (AKI) or nephrotoxicity.
References
More filters
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
TSC2 mediates cellular energy response to control cell growth and survival.
TL;DR: It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis.
Journal ArticleDOI
AMPK phosphorylation of raptor mediates a metabolic checkpoint.
Dana M. Gwinn,David B. Shackelford,Daniel F. Egan,Maria M. Mihaylova,Annabelle Mery,Debbie S. Vasquez,Benjamin E. Turk,Reuben J. Shaw +7 more
TL;DR: AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor, uncovering a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status.
Journal ArticleDOI
Autophagy and the Integrated Stress Response
TL;DR: Autophagy is a cell biological process that is a central component of the integrated stress response and can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli.
Journal ArticleDOI
TFEB links autophagy to lysosomal biogenesis.
Carmine Settembre,Chiara Di Malta,Vinicia Assunta Polito,Vinicia Assunta Polito,Moises Garcia Arencibia,Francesco Vetrini,Serkan Erdin,Serkan Erdin,Serpil Uckac Erdin,Serpil Uckac Erdin,Tuong Huynh,Tuong Huynh,Diego L. Medina,Pasqualina Colella,Marco Sardiello,Marco Sardiello,David C. Rubinsztein,Andrea Ballabio +17 more
TL;DR: A mitogen-activated protein kinase–dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles during starvation.