Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity

Abstract

The incidence and severity of metabolic diseases can be reduced by introducing healthy lifestyle habits including moderate exercise. A common observation in age-related metabolic diseases is an increment in systemic inflammation (the so-called inflammaging) where mitochondrial reactive oxygen species (ROS) production may have a key role. Exercise prevents these metabolic pathologies, at least in part, due to its ability to alter immunometabolism, e.g., reducing systemic inflammation and by improving immune cell metabolism. Here, we review how exercise regulates immunometabolism within contracting muscles. In fact, we discuss how circulating and resident macrophages alter their function due to mitochondrial signaling, and we propose how these effects can be triggered within skeletal muscle in response to exercise. Finally, we also describe how exercise-induced mitochondrial adaptations can help to fight against virus infection. Moreover, the fact that moderate exercise increases circulating immune cells must be taken into account by public health agencies, as it may help prevent virus spread. This is of interest in order to face not only acute respiratory-related coronavirus (SARS-CoV) responsible for the COVID-19 pandemic but also for future virus infection challenges.

Keywords: COVID-19; exercise; immune system; metabolic disease; mitochondria.

Figure 1

Exercise improves systemic inflammation by enhancing mitochondrial metabolism. This effect likely involves decreased mitochondrial reactive oxygen species (ROS) production below pathological levels which may ultimately affect immune cell function.

Figure 2

Exercise induces a number of structural and metabolic changes within skeletal muscle mitochondria that may affect immune function. Exercise enhances mitochondrial function by (1) inducing the assembly of respiratory complexes into supercomplexes; (2) promoting an enlargement of functional mitochondrial network; (3) increasing mitochondrial turnover and (4) reducing mitochondrial ROS production. The immunological role of skeletal muscle lipid droplets and resident macrophages in response to exercise is yet to be elucidated. Mechanistic studies, however, suggest that LDs separated from mitochondria can improve innate immune function in a mechanism likely mimicked by exercise. In addition, resident macrophages are known to improve mitochondrial function through eliminating dysfunctional parts of the mitochondrial network. As some viruses alter the innate immune system in cells by inducing excessive mitochondrial fragmentation, exercise may help to face virus infection by maintaining an enlarged and fully functional mitochondrial network. ROS, reactive oxygen species; DRP, dynamin-like protein; FIS1, fission, mitochondrial 1; MFN, mitofusin; OPA1, optic atrophy 1.