PGC-1α activation to enhance macrophage immune function in mycobacterial infections

• DOI: 10.1371/journal.pone.0310908
• Publication Date: 2025-02-06T18:27:51Z
• Authors: Joel R. Frandsen; Zhihong Yuan; Brahmchetna Bedi; Zohra Prasla; Seoung-Ryoung Choi; Prabagaran Naraya...; Ruxana T. Sadikot
• Keywords: TFAM; IRF5; PPARGC1A; Organelle biogenesis

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment potential successful outcomes. Although information exists on the clinical significance NTMs, little is known about host immune response infection. NTM infections alter macrophage mitochondrial capacity decrease ATP production, efficient response, bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) master regulator biogenesis, influencing metabolism, pathways, antioxidant response. Mitochondrial transcription A (TFAM) protein essential for DNA (mtDNA) genome stability, integrity, metabolism. Both PGC-1α TFAM regulate biogenesis activity, their disruption linked inflammatory signaling altered function. We show that causes damage disrupted bioenergetics. Mechanistically we this related attenuation expression infected macrophages. Importantly, rescuing using pharmacologic approaches restored Our results suggest enhance function provide novel approach target means combat infections.