Mitochondrial metabolic remodelling during bacterial infection: Molecular mechanisms, cellular consequences, and therapeutic opportunities.

Bacterial infections remain a major global health concern, accounting for substantial morbidity, mortality, and healthcare burden, particularly in the era of increasing antimicrobial resistance. In addition to triggering classical inflammatory pathways, bacterial infections induce profound metabolic reprogramming in host cells. A central element of this response is mitochondrial metabolic remodelling. Mitochondria, beyond their role as bioenergetic organelles responsible for oxidative phosphorylation and ATP production, function as key regulators of innate immune signalling, redox homeostasis, and cell death. During infection, they serve a dual purpose, facilitating antimicrobial defence while also contributing to inflammatory tissue damage and organ dysfunction. This review integrates current evidence on the molecular mechanisms and cellular consequences of mitochondrial remodelling during bacterial infection. We focus on six major mechanistic axes such as: inhibition of the electron transport chain and subsequent bioenergetic collapse; the shift from oxidative phosphorylation to glycolysis mediated by HIF-1α and mTOR signalling; excessive production of mitochondrial reactive oxygen species and activation of NF-κB and NLRP3 pathways; DRP1-dependent mitochondrial fragmentation with impaired fusion dynamics; mitochondrial DNA release and activation of the cGAS-STING pathway; and suppression of mitochondrial biogenesis via the PGC-1α-SIRT1-AMPK axis. Finally, we discuss emerging host-directed therapeutic strategies targeting mitochondrial metabolism and highlight the need for translational studies to validate mitochondria-centred interventions in bacterial infections.