The microbiome has emerged as a key player contributing significantly to the human physiology over the past decades. The potential microbial niche is largely unexplored in the context of exercise enhancing capacity and the related mitochondrial functions. Physical exercise can influence the gut microbiota composition and diversity, whereas a sedentary lifestyle in association with dysbiosis can lead to reduced well-being and diseases. Here, we have elucidated the importance of diverse microbiota, which is associated with an individual’s fitness, and moreover, its connection with the organelle, the mitochondria, which is the hub of energy production, signaling, and cellular homeostasis. Microbial by-products, such as short-chain fatty acids, are produced during regular exercise that can enhance the mitochondrial capacity. Therefore, exercise can be employed as a therapeutic intervention to circumvent or subside various metabolic and mitochondria-related diseases. Alternatively, the microbiome–mitochondria axis can be targeted to enhance exercise performance. This review furthers our understanding about the influence of microbiome on the functional capacity of the mitochondria and exercise performance, and the interplay between them.

Regular exercise provides several health benefits that can improve the cardiovascular and musculoskeletal systems, but clear evidence on the effect of exercise-induced hyperventilation in particulate matter (PM) exposure is still lacking. This study aimed to investigate the effects of exercise in PM exposure on reactive oxygen species (ROS) generation, inflammatory response, and mitochondrial integrity in human lung epithelial cells (A549), as well as in mouse lung tissue. In in vitro experiments, PM treatment was shown to significantly increased ROS production, and reduced cell viability and mitochondrial function in A549 cells. The mice were divided into four groups for an in vivo exercise experiment: control (CON), PM inhalation (PI), PM inhalation during exercise (PIE), and exercise (EX) groups. The PI and PIE groups were exposed to 100 μg/m³ of PM for 1 h per day for a week. The PIE and EX groups performed treadmill exercises every day for 1 h at 20 m/min for a week. The levels of pro-inflammatory markers (IL-6 and TNF-α) were significantly higher in the PI group than in the CON group (P < 0.001 and P < 0.01, respectively). The carbonyl protein level was decreased in EX vs. PI (P < 0.001). Mitochondrial fission (Drp1) content was significantly decreased in the EX vs. CON group (P < 0.01), but anti-mitochondrial fission (P-Drp1 Ser637) was increased in the EX vs. PI group (P < 0.05). Mitochondrial autophagy (mitophagy), which is an assessment of mitochondrial integrity, was markedly increased in PI vs. CON (P < 0.001), but the level was reversed in PIE (P < 0.05). Lung fibrosis was increased in PI vs. CON group (P < 0.001), however, the cells were rescued in the PIE (P < 0.001). The number of apoptotic cells was remarkably increased in the PI vs. CON group (P < 0.001), whereas the level was decreased in the PIE (P < 0.001). Taken together, these results showed that short-term exposure to PM triggers oxidative stress, pro-inflammatory responses, and apoptosis in the lungs, but the PM-induced adverse effects on the lung tissue are not exacerbated by exercise-induced PM hyperventilation but rather has a protective effect.

Cells are constantly challenged by genotoxic stresses that can lead to genome instability. The integrity of the nuclear genome is preserved by the DNA damage response (DDR) and repair. Additionally, these stresses can induce mitochondria to transiently hyperfuse; however, it remains unclear whether canonical DDR is linked to these mitochondrial morphological changes. Here, we report that the abolition of mitochondrial fusion causes a substantial defect in the ATM-mediated DDR signaling. This deficiency is overcome by the restoration of mitochondria fusion. In cells with fragmented mitochondria, genotoxic stress-induced activation of JNK and its translocation to DNA lesion are lost. Importantly, the mitochondrial fusion machinery of MFN1/MFN2 associates with Sab (SH3BP5) and JNK, and these interactions are indispensable for the Sab-mediated activation of JNK and the ATM-mediated DDR signaling. Accordingly, the formation of BRCA1 and 53BP1 foci, as well as homology and end-joining repair are impaired in cells with fragmented mitochondria. Together, these data show that mitochondrial fusion-dependent JNK signaling is essential for the DDR, providing vital insight into the integration of nuclear and cytoplasmic stress signals.

Summary Avenanthramide C (AVC), found mainly in oats, mediates anti-inflammatory activities by reducing the anti-inflammatory cytokine levels. This study investigated the effects of AVC on hypoxia-induced cyclooxygenase-2 (COX-2) expression in A549 cells. AVC suppressed the hypoxia-induced increase in COX-2 protein levels and promoter activity. We also observed that the effects of AVC were reversed by a SIRT1 inhibitor, indicating that the inhibitory effects of AVC on hypoxia-induced COX-2 expression are mediated by SIRT1. Therefore, AVC inhibits the hypoxic induction of COX-2 expression via SIRT1 activation. Our results suggest that AVC could be beneficial for preventing lung inflammation under hypoxia.