Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis

Abstract

Skeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise.

Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria

“…PGC‐1β, another transcription factor, shares similar molecular structure and function with PGC‐1α, including nuclear receptor binding and transcriptional activation, and also regulates MB through shared mechanisms with PGC‐1α, such as activating Nrf‐1 . The nuclear respiratory factors (Nrf‐1/Nrf‐2) are associated with the expression of multiple mitochondrial proteins, such as OXPHOS complex proteins, enzymes of haeme biosynthesis and proteins involved in mitochondrial import of nuclear‐encoded subunits . Nrf‐1 transcription is regulated also by PPAR‐β in muscle of exercised rats, a mechanism that increases MB through upregulation of AMP‐activated protein kinase (AMPK) and Nrf‐1/Nrf‐2 that integrate their effects on the nuclear genes of MB with promotion of the replication and transcription of TFAM.…”

“…2 The nuclear respiratory factors (Nrf-1/ Nrf-2) are associated with the expression of multiple mitochondrial proteins, such as OXPHOS complex proteins, enzymes of haeme biosynthesis and proteins involved in mitochondrial import of nuclear-encoded subunits. 19,20 Nrf-1 transcription is regulated also by PPAR-β in muscle of exercised rats, a mechanism that increases MB through upregulation of AMP-activated protein kinase (AMPK) and Nrf-1/Nrf-2 that integrate their effects on the nuclear genes of MB with promotion of the replication and transcription of TFAM. The latter is a multifunctional protein that belongs to the high-mobility group (HMG) proteins that are characterized by their ability to bend, wrap and unwind mtDNA without sequence specificity, but with preferential interaction with some identified regions.…”

Age-related changes in skeletal muscle mitochondria: the role of exercise

“…To prevent age-related decline in skeletal muscle, some studies have focused on targeting the mitochondria. It is widely suggested that exercise training may reduce mitochondrial ROS because exercise can increase the antioxidant capacity in muscles 26, 27…”

Exercise effects on physiological function during aging

“…Besides stimulating the DNA binding of nuclear factors, PGC-1α activates mitochondrial transcription factor A (TFAM), which is essential for gene expression from mtDNA [31]. During exercise, PGC-1α can be activated by AMP-activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (SIRT1), Ca 2+ /calmodulin-dependent protein kinase IV, calcineurin A, and ROS [32,33]. But PGC-1α is not just activated by ROS, it can control the level of ROS partly through the activation of nuclear factor (erythroid-derived 2)-like 2 that binds to antioxidant response element (ARE) [34].…”