Irisin and Autophagy: First Update

Abstract

Aging and sedentary life style are considered independent risk factors for many disorders. Under these conditions, accumulation of dysfunctional and damaged cellular proteins and organelles occurs, resulting in a cellular degeneration and cell death. Autophagy is a conserved recycling pathway responsible for the degradation, then turnover of cellular proteins and organelles. This process is a part of the molecular underpinnings by which exercise promotes healthy aging and mitigate age-related pathologies. Irisin is a myokine released during physical activity and acts as a link between muscles and other tissues and organs. Its main beneficial function is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis. Irisin modulates metabolic processes, acting on glucose homeostasis, reduces systemic inflammation, maintains the balance between resorption and bone formation, and regulates the functioning of the nervous system. Recently, some of its pleiotropic and favorable properties have been attributed to autophagy induction, posing irisin as an important regulator of autophagy by exercise. This review article proposes to bring together for the first time the “state of the art” knowledge regarding the effects of irisin and autophagy. Furthermore, treatments on relation between exercise/myokines and autophagy have been also achieved.

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

“…Autophagy, as a potent cell strategy for protecting against in-flammation, has been proposed as a mechanism by which physical exercise mediates its beneficial effects on health. In accordance with this hypothesis, several reports showed that exercise could trigger autophagy in different tissues and organs [65]. Importantly, in the AD mice model, the genetically-induced hyperactivation of autophagy, by knock-in of a point mutation in the gene Beclin/Becn1, which is essential in autophagy, resulted in the decrease of amyloid accumulation and limitation of cognitive decline.…”

“…In particular, irisin activated Opa1 -induced mitophagy, and this event preserved mitochondrial function, decreased oxidative stress, and inhibited apoptosis of cardiomyocytes following myocardial infarction [ 67 ]. Therefore, this irisin shielding mechanism [ 65 ] can be added to the other described effects of the myokine, underlying the importance of irisin in alleviating neuroinflammatory responses and neurodegenerative diseases.…”

Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin

“…A recent interesting discovery about Irisin function is related to autophagy (reviewed extensively in Pesce et al, 2020). Autophagy is an intracellular process that occurs to eliminate misfolded proteins and injured organelles, and in general to maintain the cellular homeostasis (reviewed in Glick et al, 2010).…”

“…Autophagy is also involved in the pathology of neurodegenerative disorders such as AD, amyotrophic lateral sclerosis (ALS), and familial Parkinson's disease (PD) (Nixon, 2013). Recent studies have shown that exercise stimulates autophagy in a variety of tissues, including skeletal muscles (Salminen and Vihko, 1984;Grumati et al, 2011), and several myokines have been recognized as autophagy regulators (Pesce et al, 2020). Irisin has been associated to autophagy induction in several cell types including myocytes, cardiomyocytes (Li et al, 2018), and hepatocytes (Bi et al, 2019(Bi et al, , 2020.…”

Addendum: Pesce et al. Irisin and Autophagy: First Update. Int. J. Mol. Sci. 2020, 21, 7587

“…We did not receive the copyright for Figure 2 in our published paper [ 1 ]. Now, we have received it from the correspondence author Ewa Pocheć [ 2 ].…”