The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
1
Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
2
Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
3
Hepatitis (HCV/HBV/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN 37614, USA
*
Author to whom correspondence should be addressed.
Cells 2021, 10(1), 174; https://doi.org/10.3390/cells10010174
Received: 22 December 2020 / Revised: 12 January 2021 / Accepted: 14 January 2021 / Published: 16 January 2021
(This article belongs to the Special Issue Mechanisms of Aging and Therapeutic Approaches to Target Age-Associated Chronic Diseases)
According to the WHO, 38 million individuals were living with human immunodeficiency virus (HIV), 25.4 million of which were using antiretroviral therapy (ART) at the end of 2019. Despite ART-mediated suppression of viral replication, ART is not a cure and is associated with viral persistence, residual inflammation, and metabolic disturbances. Indeed, due to the presence of viral reservoirs, lifelong ART therapy is required to control viremia and prevent disease progression into acquired immune deficiency syndrome (AIDS). Successful ART treatment allows people living with HIV (PLHIV) to achieve a similar life expectancy to uninfected individuals. However, recent studies have illustrated the presence of increased comorbidities, such as accelerated, premature immune aging, in ART-controlled PLHIV compared to uninfected individuals. Studies suggest that both HIV-infection and ART-treatment lead to mitochondrial dysfunction, ultimately resulting in cellular exhaustion, senescence, and apoptosis. Since mitochondria are essential cellular organelles for energy homeostasis and cellular metabolism, their compromise leads to decreased oxidative phosphorylation (OXPHOS), ATP synthesis, gluconeogenesis, and beta-oxidation, abnormal cell homeostasis, increased oxidative stress, depolarization of the mitochondrial membrane potential, and upregulation of mitochondrial DNA mutations and cellular apoptosis. The progressive mitochondrial damage induced by HIV-infection and ART-treatment likely contributes to accelerated aging, senescence, and cellular dysfunction in PLHIV. This review discusses the connections between mitochondrial compromise and cellular dysfunction associated with HIV- and ART-induced toxicities, providing new insights into how HIV and current ART directly impact mitochondrial functions and contribute to cellular senescence and aging in PLHIV. Identifying this nexus and potential mechanisms may be beneficial in developing improved therapeutics for treating PLHIV.
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Keywords:
HIV; ART; mitochondria; mtDNA; ROS; cellular dysfunction
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MDPI and ACS Style
Schank, M.; Zhao, J.; Moorman, J.P.; Yao, Z.Q. The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging. Cells 2021, 10, 174. https://doi.org/10.3390/cells10010174
AMA Style
Schank M, Zhao J, Moorman JP, Yao ZQ. The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging. Cells. 2021; 10(1):174. https://doi.org/10.3390/cells10010174
Chicago/Turabian StyleSchank, Madison; Zhao, Juan; Moorman, Jonathan P.; Yao, Zhi Q. 2021. "The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging" Cells 10, no. 1: 174. https://doi.org/10.3390/cells10010174
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