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Recent surge of studies indicate their regulatory role in meeting energy demands in renal cells making them critical entities in the progression of diabetic nephropathy. Diabetes is remarkably associated with abnormal fuel metabolism, a basis for free radical generation, which if left unchecked may devastate the mitochondria structurally and functionally. Impaired mitochondrial function and their aberrant accumulation have been known to be involved in the manifestation of diabetic nephropathy, indicating perturbed balance of mitochondrial dynamics, and mitochondrial turnover. Mitochondrial dynamics emphasize the critical role of mitochondrial fission proteins such as mitochondrial fission 1, dynamin\u2010related protein 1 and mitochondrial fission factor and fusion proteins including mitofusin\u20101, mitofusin\u20102 and optic atrophy 1. Clearance of dysfunctional mitochondria is aided by translocation of autophagy machinery to the impaired mitochondria and subsequent activation of mitophagy regulating proteins PTEN\u2010induced putative kinase 1 and Parkin, for which mitochondrial fission is a prior event. In this review, we discuss recent progression in our understanding of the molecular mechanisms targeting reactive oxygen species mediated alterations in mitochondrial energetics, mitophagy related disorders, impaired glucose transport, tubular atrophy, and renal cell death. The molecular cross talks linking autophagy and renoprotection through an intervention of 5\u2032\u2010AMP\u2010activated protein kinase, mammalian target of rapamycin, and SIRT1 factors are also highlighted here, as in\u2010depth exploration of these pathways may help in deriving therapeutic strategies for managing diabetes provoked end\u2010stage renal disease.<\/jats:p>","DOI":"10.1002\/jcp.28712","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T06:30:43Z","timestamp":1556519443000},"page":"19223-19236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Critical role of mitochondrial dysfunction and impaired mitophagy in diabetic nephropathy"],"prefix":"10.1002","volume":"234","author":[{"given":"Sugandh","family":"Saxena","sequence":"first","affiliation":[{"name":"Herbal Research Laboratory CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR) Lucknow 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