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Curr Pharm Des. 2019;25(23):2584-2594. doi: 10.2174/1381612825666190718153901.

An Overview on ATP Dependent and Independent Proteases Including an Anterograde to Retrograde Control on Mitochondrial Function; Focus on Diabetes and Diabetic Complications.

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Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, India.


Mitochondria are the central power stations of the cell involved with a myriad of cell signalling pathways that contribute for whole health status of the cell. It is a well known fact that not only mitochondrial genome encodes for mitochondrial proteins but there are several other mitochondrial specific proteins encoded by nuclear genome which regulate plethora of cell catabolic and anabolic process. Anterograde pathways include nuclear gene encoded proteins and their specific transport into the mitochondria and regulation of mitochondrial homeostasis. The retrograde pathways include crosstalk between the mitochondria and cytoplasmic proteins. Indeed, ATP dependent and independent proteases are identified to be very critical in balancing anterograde to retrograde signalling and vice versa to maintain the cell viability or cell death. Different experimental studies conducted on silencing the genes of these proteases have shown embryonic lethality, cancer cells death, increased hepatic glucose output, insulin tolerance, increased protein exclusion bodies, mitochondrial dysfunction, and defect in mitochondrial biogenesis, increased inflammation, Apoptosis etc. These experimental studies included from eubacteria to eukaryotes. Hence, many lines of theories proposed these proteases are conservative from eubacteria to eukaryotes. However, the regulation of these proteases at gene level is not clearly understood and still research is warranted. In this review, we articulated the origin and regulation of these proteases and the cross talk between the nucleus and mitochondria vice versa, and highlighted the role of these proteases in diabetes and diabetic complications in human diseases.


ATP dependent and independent proteases; Diabetes; anterograde pathways; apoptosis; mitochondrial dysfunction; mitochondrial genome.

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