生物医学に関する洞察 オープンアクセス

抽象的な

Role of Cx43 and SLC25A51 Transporters-New Perspectives in NAD+ Supplementation to Improve Mitochondrial Performance

Bamboo XZ Yan, WeiGuo Lao, Chi Zhang, Thombas Ebjer ,Hina Asrar

NAD⁺ , a linchpin for mitochondrial function, is crucial in protecting the body from aging and related diseases. The reduced biosynthesis and increased activity of NAD⁺ consuming enzymes lower cellular contents of NAD⁺ with aging. Since the homeostasis of the NAD⁺ pools is vulnerable to biological aging, and thus, raises a serious concern for the healthcare staff to cure age-related disorders. Replenishing NAD⁺ pools with the administration of relevant supplements rescues the depleting cellular NAD⁺. Accordingly, the small-scale human clinical trials have shown ameliorative effects of exogenous NAD⁺ in treating age-related disorders. However, validation of these studies requires considerable time. Therefore, investigations on a rapid and targeted influx of NAD⁺ are fundamental to achieving the benefits offered by the science of anti-aging. One possible strategy is the oral administration of intact NAD⁺ molecule followed by its forced localization to the mitochondria as an elixir of longevity. Integration of the recent findings with previous studies to dissect the trafficking of intracellular NAD⁺ will direct to a heuristic approach to extending individual lifespan. Here we present a critical analysis of the current status of therapeutic interventions to enhance intracellular NAD⁺ while highlighting the controversial studies and gaps in the same field. This review emphasizes using a connexion (Cx43) and mitochondrial carrier family (SLC25A51) as the chief NAD⁺ transporters and the possible erspectives to translate this knowledge for better mitochondrial efficiency. We propose a strategy based on an improved influx of mitochondrial NAD⁺ that will restore the redox and non-redox functions of NAD⁺. This understanding may establish a foundation to smartly deal with situations where the inability to import the supplemented NAD⁺ is the prime cause of mitochondria performance-related diseases.