Host miRNA orchestration of mitophagy pathways during bacterial infection: current advances and future directions

Abstract

Pathogenic bacterial infections continue to impose a substantial global health burden. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as critical post-transcriptional regulators of host innate immunity and inflammatory responses during bacterial pathogenesis. Accumulating evidence indicates that miRNAs dictate the outcomes of infection by orchestrating fundamental cellular processes, notably mitophagy—a selective autophagic pathway essential for mitochondrial quality control and cytosolic surveillance. While recent studies have begun to elucidate the molecular interplay between miRNA biogenesis and mitophagy regulation, the mechanistic crosstalk between miRNAs and mitophagy during bacterial infection remains fragmentary, and many reported miRNA-mitophagy regulatory relationships are derived from non-infectious disease models rather than bacterial infection settings. In this review, we synthesize current advances regarding miRNA-mediated modulation of core mitophagy machinery and associated signaling cascades in the context of bacterial infection. We further explore the pathophysiological implications of these regulatory networks and evaluate the therapeutic potential of targeting specific miRNA–mitophagy axes. This study provides mechanistic insights into how host miRNAs reprogram mitophagy to combat infection and the miRNA–mitophagy axis maybe as a promising dual-targeted therapeutic strategy for the development of host-directed therapies against bacterial diseases.