The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics

Abstract

Mitochondria are intracellular organelles that utilize nutrients to generate energy in the form of ATP by oxidative phosphorylation. Mitochondrial DNA (mtDNA) in humans is a 16,569 base pair double-stranded circular DNA that encodes for 13 vital proteins of the electron transport chain. Our understanding of the mitochondrial genome’s transcription, translation, and maintenance is still emerging, and human pathologies caused by mtDNA dysfunction are widely observed. Additionally, a correlation between declining mitochondrial DNA quality and copy number with organelle dysfunction in aging is well-documented in the literature. Despite tremendous advancements in nuclear gene-editing technologies and their value in translational avenues, our ability to edit mitochondrial DNA is still limited. In this review, we discuss the current therapeutic landscape in addressing the various pathologies that result from mtDNA mutations. We further evaluate existing gene therapy efforts, particularly allotopic expression and its potential to become an indispensable tool for restoring mitochondrial health in disease and aging.

Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep

“…The telomere length, a marker of biological aging [ 73 ], was also not significantly affected in response to prenatal BPA exposure. Similarly, mitochondrial DNA copy number (mtDNA-CN), associated with several aging-related diseases [ 74 , 75 ] and lipofuscin accumulation, was not affected by prenatal BPA exposure and is represented in Figure 4 .…”

“…associated with several aging-related diseases [74,75] and lipofuscin accumulation, was not affected by prenatal BPA exposure and is represented in Figure 4. associated with several aging-related diseases [74,75] and lipofuscin accumulation, was not affected by prenatal BPA exposure and is represented in Figure 4.…”

Mitochondrial Deoxyribonucleic Acid (mtDNA), Maternal Inheritance, and Their Role in the Development of Cancers: A Scoping Review

“…A recent hypothesis also suggested that the mitochondria may under the influence of microbial pathogens can transform themselves into super-power cells or immortal cancer cells that enable tumor formation [ 55 ]. In view of the potential role of mtDNA in aging and diseases including cancers, the role of gene editing in therapeutic management was being explored [ 56 ].…”

Асоціація Мітохондріальних Гаплотипів З Фенотиповими Ознаками Відгодівельної Продуктивності Гібридних Свиней

“…Серія «Тваринництво», випуск 2 (49), 2022 of the electron transport chain, 22 tRNAs and 2 rRNAs (Hieu Duc Nguyen, 2017; Anjana Saravanan, 2022). The mitochondrial genome has one major non-coding region -the D-loop, which is where the transcription and replication factors encoded by the kernel interact, which travel to the mitochondria to initiate transcription, and then replication of the mitochondrial genome.…”