Pharmacological approaches to restore mitochondrial function

Because resveratrol activates mitochondrial biogenesis through the AMPK-SIRT1-PGC1α axis, it prompts mitochondrial biogenesis, the unfolded protein response, and autophagy machinery that are known to extend longevity in animals.

“Because resveratrol activates mitochondrial biogenesis through the AMPK-SIRT1-PGC1α axis, it prompts mitochondrial biogenesis, the unfolded protein response, and autophagy machinery that are known to extend longevity in animals (37, 249).”

Synthetic PPARβ/δ agonists such as GW501516 or L-165041 reduce adiposity, improve insulin sensitivity and hyperlipidemia in obese patients, through their ability to augment mitochondrial biogenesis and activity.

“Similarly, synthetic PPARβ/δ agonists such as GW501516 or L-165041 reduce adiposity improve insulin sensitivity and hyperlipidemia in obese patients, through their ability to augment mitochondrial biogenesis and activity (249).”

Mitochondrial dysfunction is at the center of many metabolic disorders, such as obesity and type 2 diabetes mellitus.

“Mitochondrial dysfunction is at the center of many metabolic disorders, such as obesity and type 2 diabetes mellitus (T2DM) (Andreux et al, 2013).”

Several pharmacological and nutritional interventions protect against the development of insulin resistance and high-fat diet-induced metabolic damage.

“Several pharmacological and nutritional interventions have been designed in this direction, which protect against the development of insulin resistance and high-fat diet (HFD)-induced metabolic damage (e.g., resveratrol or PPARβ agonists) (Andreux et al, 2013).”

Mitochondrial biogenesis is achieved through orchestrated induction of several transcriptional regulators whose activity is critically determined by energetic demands.

“Mitochondrial biogenesis is achieved through orchestrated induction of several transcriptional regulators, whose activity is critically determined by energetic demands (Andreux et al, 2013) (Figs 2B, 3B and C).”

PGC-1α coactivates a set of transcription factors involved in mitochondrial metabolism, including estrogen-related receptors, nuclear respiratory factors, and PPARs.

“As a consequence, PGC-1α coactivates a set of transcription factors involved in mitochondrial metabolism, including estrogen-related receptors, nuclear respiratory factors, and PPARs (Andreux et al, 2013).”

PGC-1α and NCoR1 oppositely regulate several transcription factors, including nuclear respiratory factors, estrogen-related receptors and PPARs.

“In fact, PGC-1α and NCoR1 oppositely regulate several transcription factors, including nuclear respiratory factors, estrogen-related receptors and PPARs (Scarpulla, 2011; Andreux et al, 2013; Mottis et al, 2013).”

Loss of mitochondrial number and activity characterizes several inherited mitochondrial diseases and age-related neurodegenerative and metabolic disorders.

“Reductions in mitochondrial number and activity are a hallmark of several inherited mitochondrial diseases, as well as a number of age-related neurodegenerative and metabolic disorders (Andreux et al., 2013).”