Abstract
Aging is a general degenerative process related to deterioration of cell functions in the entire organism. Mitochondria, which play a key role in energy homeostasis and metabolism of reactive oxygen species (ROS), require lifetime control and constant renewal. This explains recently peaked interest in the processes of mitochondrial biogenesis and mitophagy. The principal event of mitochondrial metabolism is regulation of mitochondrial DNA (mtDNA) transcription and translation, which is a complex coordinated process that involves at least two systems of transcription factors. It is commonly believed that its major regulatory proteins are PGC-1α and PGC-1β, which act as key factors connecting several regulator cascades involved in the control of mitochondrial metabolism. In recent years, the number of publications on the essential role of Nrf2/ARE signaling in the regulation of mitochondrial biogenesis has grown exponentially. Nrf2 is induced by various xenobiotics and oxidants that oxidize some Nrf2 negative regulators. Thus, ROS, in particular H2O2, were found to be strong Nrf2 activators. At present, there are two major concepts of mitochondrial biogenesis. Some authors suggest direct involvement of Nrf2 in the regulation of this process. Others believe that Nrf2 regulates expression of the antioxidant genes, while the major and only regulator of mitochondrial biogenesis is PGC-1α. Several studies have demonstrated the existence of the regulatory loop involving both PGC-1α and Nrf2. In this review, we summarized recent data on the Nrf2 role in mitochondrial biogenesis and its interaction with PGC-1α in the context of extending longevity.
Highlights
Mitochondria play a key role in the pathogenesis of many diseases (Wallace, 2005; Lin and Beal, 2006; Lindblom et al, 2015; Ratliff et al, 2016; Boengler et al, 2017) and aging (Jang et al, 2018)
Studies based on electron microscopy have not shown any age-related changes in the number of mitochondria in skeletal muscle (Mathieu-Costello et al, 2005; Callahan et al, 2014)
Opposite conclusions made by various research groups may be associated with different methods for determining the number of mitochondria, and with structural, biochemical and functional heterogeneity of skeletal muscles (Hepple, 2014)
Summary
Popov VN (2019) Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf and PGC-1α. Mitochondria, which play a key role in energy homeostasis and metabolism of reactive oxygen species (ROS), require lifetime control and constant renewal. This explains recently peaked interest in the processes of mitochondrial biogenesis and mitophagy. It is commonly believed that its major regulatory proteins are PGC-1α and PGC-1β, which act as key factors connecting several regulator cascades involved in the control of mitochondrial metabolism. We summarized recent data on the Nrf role in mitochondrial biogenesis and its interaction with PGC-1α in the context of extending longevity
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