New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy.

Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.

Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line.

It has become amply clear that mitochondrial function defined by quality, quantity, dynamics, homeostasis, and regulated by mitophagy and mitochondrial biogenesis is a critical metric of human aging and disease. As a consequence, therapeutic interventions that can improve mitochondrial function can have a profound impact on human health and longevity. Kisspeptins are neuropeptides belonging to the family of metastasis suppressors that are known to regulate functions like fertility, reproduction, and metabolism. Using SKNSH cell line, hippocampus explant cultures and hippocampus of aging Wistar rat models, we show that Kisspeptin-10 (Kp) induces autophagy and mitophagy via calcium, Ca2+/CaM-dependent protein kinase kinase ß (CaMKKß), AMP-activated protein kinase (AMPK), and Unc-51 like autophagy activating kinase (ULK1) signaling pathway that is independent of mammalian target of rapamycin (mTOR). Intriguingly, Kp administration in vivo also results in the enhancement of mitochondrial number, complex I activity, and Adenosine Triphosphate (ATP) levels. This study uncovers potential effects of Kp in protecting mitochondrial health and as a possible therapeutic intervention to hippocampus associated impairments such as memory, cognitive aging, and other diseases linked to mitochondrial dysfunction.