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Review Article

Mitochondrial-induced Epigenetic Modifications: From Biology to Clinical Translation

[ Vol. 27 , Issue. 2 ]

Author(s):

Jahnavi Sharma, Roshani Kumari, Arpit Bhargava, Rajnarayan Tiwari and Pradyumna K. Mishra*   Pages 159 - 176 ( 18 )

Abstract:


Mitochondria are maternally inherited semi-autonomous organelles that play a central role in redox balance, energy metabolism, control of integrated stress responses, and cellular homeostasis. The molecular communication between mitochondria and the nucleus is intricate and bidirectional in nature. Though mitochondrial genome encodes for several key proteins involved in oxidative phosphorylation, several regulatory factors encoded by nuclear DNA are prominent contributors to mitochondrial biogenesis and function. The loss of synergy between this reciprocal control of anterograde (nuclear to mitochondrial) and retrograde (mitochondrial to nuclear) signaling, triggers epigenomic imbalance and affects mitochondrial function and global gene expressions. Recent expansions of our knowledge on mitochondrial epigenomics have offered novel perspectives for the study of several non-communicable diseases including cancer. As mitochondria are considered beacons for pharmacological interventions, new frontiers in targeted delivery approaches could provide opportunities for effective disease management and cure through reversible epigenetic reprogramming. This review focuses on recent progress in the area of mitochondrial-nuclear cross-talk and epigenetic regulation of mitochondrial DNA methylation, mitochondrial micro RNAs, and post-translational modification of mitochondrial nucleoid-associated proteins that hold major opportunities for targeted drug delivery and clinical translation.

Keywords:

Mitochondrial targeting, mitochondrial medicine, mitochondrial-nuclear cross-talk, epigenomic signatures, translational research, DNA methylation.

Affiliation:

Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal



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