Is the NDUFV2 subunit of the hydrophilic complex I domain a key determinant of animal longevity?

• Published in: The FEBS journal 2021-12, Vol.288 (23), p.6652-6673
• Main Authors: Pamplona, Reinald, Jové, Mariona, Mota‐Martorell, Natalia, Barja, Gustavo
• Format: Article
• Language: English
• Subjects: Aging; Aging - genetics; Aging - metabolism; animal longevity; Animals; Bioenergetics; Biological Evolution; complex I; Electron transfer; Electron transport; Electron Transport - genetics; Electron transport chain; Electron Transport Complex I - genetics; Electron Transport Complex I - metabolism; Energy Metabolism - genetics; Free radicals; Free Radicals - metabolism; Gene expression; Longevity; Longevity - genetics; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Modules; N1a cluster; NDUFV2 subunit; Oxygen Consumption - genetics; Phenotypes; Protein Subunits - genetics; Protein Subunits - metabolism; reactive oxygen species; Structure-function relationships; superoxide radical
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.15714

Complex I, a component of the electron transport chain, plays a central functional role in cell bioenergetics and the biology of free radicals. The structural and functional N module of complex I is one of the main sites of the generation of free radicals. The NDUFV2 subunit/N1a cluster is a component of this module. Furthermore, the rate of free radical production is linked to animal longevity. In this review, we explore the hypothesis that NDUFV2 is the only conserved core subunit designed with a regulatory function to ensure correct electron transfer and free radical production, that low gene expression and protein abundance of the NDUFV2 subunit is an evolutionary adaptation needed to achieve a longevity phenotype, and that these features are determinants of the lower free radical generation at the mitochondrial level and a slower rate of aging of long‐lived animals. Mitochondrial complex I is key in cell bioenergetics and biology of free radicals. The N module of complex I is a place of reactive oxygen species (ROS) generation. The NDUFV2 subunit is a component of this module. The rate of ROS production is linked to animal longevity. This review proposes that the abundance of the NDUFV2 subunit is determinant of ROS production and the aging rate of animals.