Mitochondrial microRNA (MitomiRs) in cancer and complex mitochondrial diseases: current status and future perspectives
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Cellular and Molecular Life Sciences
REVIEW
Mitochondrial microRNA (MitomiRs) in cancer and complex mitochondrial diseases: current status and future perspectives Paresh Kumar Purohit1,2 · Neeru Saini1,2 Received: 2 May 2020 / Revised: 13 September 2020 / Accepted: 5 October 2020 © Springer Nature Switzerland AG 2020
Abstract Mitochondria are not only important for cellular bioenergetics but also lie at the heart of critical metabolic pathways. They can rapidly adjust themselves in response to changing conditions and the metabolic needs of the cell. Mitochondrial involvement as well as its dysfunction has been found to be associated with variety of pathological processes and diseases. mitomiRs are class of miRNA(s) that regulate mitochondrial gene expression and function. This review sheds light on the role of mitomiRs in regulating different biological processes—mitochondrial dynamics, oxidative stress, cell metabolism, chemoresistance, apoptosis,and their relevance in metabolic diseases, neurodegenerative disorders, and cancer. Insilico analysis of predicted targets of mitomiRs targeting energy metabolism identified several significantly altered pathways (needs in vivo validations) that may provide a new therapeutic approach for the treatment of human diseases. Last part of the review discusses about the clinical aspects of miRNA(s) and mitomiRs in Medicine. Keywords microRNA · mitomiR · Metabolic disorders · Cancer · Diabetes · Neurodegenerative disorders · Cardiovascular disease · Clinical medicine Abbreviations MitomiR Mitochondrial microRNA miRISC MiRNA inducing silencing complex TOM Outer membrane transporter TIM Inner membrane transporters P-bodies Processing bodies RNAi RNA interference AGO Argonaute PNPase Polynucleotide phosphorylase TCA Tricarboxylic acid ETC Electron transport chain T2DM Type 2 diabetes mellitus CRAT Carnitine O-acetyltransferase PPARδ Peroxisome proliferator-activated receptor δ Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-020-03670-0) contains supplementary material, which is available to authorized users. * Neeru Saini [email protected] 1
Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
Academy of Scientific and Innovative Research, (AcSIR), Ghaziabad 201 002, India
2
ROS Reactive oxygen species VDAC Voltage-dependent anion channel GLUT Glucose transporter TNFα Tumor necrosis factor-alpha APP Amyloid precursor protein TFAM Mitochondrial transcription factor NRF Nuclear respiratory factor SOD Superoxide dismutase GPX Glutathione peroxidase TrxR Thioredoxinreductase SDHD Succinate dehydrogenase subunit D COX Cytochrome oxidase HIF Hypoxia-inducible factor GalNAc N-Acetylgalactosamine HCV Hepatitis c virus BDNF Brain-derived neurotrophic factor VEGF Vesicular endothelial growth factor
Introduction Mitochondria are dynamic double-membrane organelles that produce power to the cell’s biochemical reactions. Their role in
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