Cui, Kangli (2024) Human skeletal muscle transcriptomic analysis of pathways associated with autophagy and mitophagy in response to a single session of high-intensity interval exercise in hypoxia. Research Master thesis, Victoria University.

Abstract

Autophagy/mitophagy are cellular processes that play pivotal roles in maintaining mitochondrial function; thus, understanding their responses to high-intensity interval exercise (HIIE) can provide insights into the overall adaptive mechanisms of skeletal muscle. This study aimed to investigate the effects of a single session of HIIE with and without hypoxia on transcriptomic response relating to autophagy/mitophagy. Ten healthy males (age: 26 ± 4 years; BMI: 23.3 ± 2) participated in three HIIE sessions randomly order: hypoxia (HY, simulated altitude of 3200m with an oxygen fraction of 0.14), normoxia matched to the relative intensity of hypoxia (NR), and normoxia matched to the absolute intensity of hypoxia (NA). Skeletal muscle samples were collected at fourtime points: before HIIE (B), immediately post-HIIE (P0H), 3 hours post-HIIE (P3H), and 24 hours post-HIIE (P24H). Transcriptomic analysis was employed to identify broad patterns in gene expression related to autophagy/mitophagy in skeletal muscle. The largest number of differentially expressed genes was observed in hypoxia after exercise 24 hours. PCA analysis did not show any significant difference between exercise conditions. Autophagy-animal and mitophagy-animal pathways (not ranked in the top 20) were significantly enriched only in hypoxia 24 hours post-exercise, and the key signaling pathway (mTOR signaling pathway) did not exhibit pronounced changes at all conditions after HIIE. To focus on autophagy/mitophagy-related genes/pathways, I chose 604 genes related to autophagy/mitophagy as target genes to perform differential expression analysis. Again, the largest number of differentially expressed genes related to autophagy/mitophagy was observed in hypoxia after exercise 24 hours. However, recognized autophagy markers such as LC3II, LC3II/LC3I ratio, P62, and mitophagy receptors (NIX, BNIP3) did not show significant differences in expression level in all conditions, and mitophagy receptor FUNDC1 was observed in hypoxia, indicating a lack of robust change in autophagy/mitophagy after a single session of HIIE with and without hypoxia. Similar expression patterns were only observed between different time points under the same exercise condition. Although our result suggests an elevated level of genes related to autophagy/mitophagy pathways under hypoxia exercise, it did not correlate with physiological performance, as a higher percentage of HRpeak and V̇ O2peak, and a higher RPE were observed in both NR and HY compared to NA. Furthermore, the increased gene expression level in hypoxia is likely affected by time points after exercise. Our result suggests that activation of autophagy/mitophagy pathways is unlikely to be responsible for the difference in observed physiological response.

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