4.2 Energy metabolism
(1) Mitochondrial dysfunction
“Oxidative phosphorylation” enables the generation of ATP in the
mitochondrial inner membrane and is the main source of energy in
eukaryotes. It is generally accepted that hypoxia or ischemia inhibits
mitochondrial oxidative phosphorylation and reduces the overall
efficiency of energy
metabolism(Cerretelli& Gelfi 2011). We
found that all 34 DEP of “Oxidative phosphorylation” were
downregulated (Fig. 2 ), indicating that the coupling reaction
of ADP and inorganic phosphate to ATP through the respiratory chain was
inhibited to a certain extent. It also reflected that reduced locomotion
powered by skeletal muscle might pose a minimal threat to survival under
hypoxia when swimming activity will be minimized.
Meanwhile we found that downregulated expression of the regulator of
mitochondrial biogenesis (PPRC1, GFM1, LONP1, SERAC1) and the downstream
mitochondrial related functional gene/proteins (COX1/2/4, Mt-Cyb,
miR-457a/15b-UQCRC2, UQCRC1, CYC1, Cyb561a3,
miR-457a/338/15b/PC-7236-ATP5A1, ATP5B), whichsuggested that
mitochondria may be dysfunctional.
(Table 1 and Fig. 5 ). Such
mitochondrial damage induced by hypoxia may lead to the production of
ROS and the decline of membrane potential of mitochondria,
causing a metabolic disorder and
apoptosis (Wang et al. 2019).
(2) Catabolism and anabolism
P. vachelli has been shown to have an acute response to hypoxia,
including activation of catabolic capacity for more energy, and
reduction of biosynthetic capacity to reduce energy expenditure in
liver. Similar results are found in P. vachelli muscles, for
example, upregulation of
PPARα/β is involved in
lipid metabolism and lipid oxidation
of skeletal muscle in low oxygen environments
(A. et al. 2018)(Table 1 ).
Also
hypoxia
induces the activation of riboflavin catabolism through upregulation of
RFK as the key enzyme, which improves carbohydrate, lipid, amino acid
metabolism in low oxygen environments(Wanget al. 2014). In this study,
we also found ample evidence of significantly increased catabolism inP. vachelli muscles. The transport-related enriched pathways
(e.g., SNARE interactions in vesicular transport, and ABC transporters)
and catabolic pathways (e.g., pyrimidine metabolism, central carbon
metabolism in cancer) contained a large proportion of upregulated genes
(Fig. 2A and 2C ). Furthermore,
we found a significant decrease in
intermediate metabolites in catabolism in metabolome KEGG analysis
(e.g., Metabolic pathways,
Glutathione, Purine and Linoleic acid metabolism), which indicated that
the consumption of these intermediate metabolites under hypoxia exceeds
their synthesis (Fig. 2C ).
Furthermore, the upregulated intermediate metabolites were a big part
among anabolic pathways (e.g., biosynthesis of aminoacyl-tRNA, plant
hormone, alkaloids derived from histidine, purine, ornithine, lysine and
nicotinic acid) in this study (Fig. 2C ). This indicated that
consumption of these intermediate metabolites was reduced and
accumulated. Additionally, we identified a large portion of
downregulated genes/proteins enriched in amino acid
biosynthesis pathways (e.g.,
aminoacyl-tRNA, ribosome,
tryptophan, lysine, cysteine, and
methionine). These results confirmed the downregulation of anabolism in
fish muscle induced by hypoxia, especially in amino acid synthesis
(Hardy et al. 2013)(Fig.
2A and 2B ).