Organelle interplay in host responses and mycobacterial resilience

Abstract Mycobacteria exploit host organelles to survive and proliferate within the intracellular environment. In parallel, host cells rely on these organelles to ensure essential biological functions and mount effective immune defenses against invading pathogens. The dynamic competition between host and mycobacteria for control of these organelles represents a central battleground in infection biology and is of increasing scientific interest. Important organelles such as mitochondria, the endoplasmic reticulum, and the Golgi apparatus play pivotal roles in determining the outcome of infection and can tip the balance between pathogen clearance and intracellular survival. Beyond their classical functions in energy production, calcium homeostasis, and protein trafficking, these structures actively participate in immune signaling, metabolism reprogramming, and inflammatory responses. Consequently, they function as powerful defenders against pathogens and, under certain conditions, represent unintentional allies. This review categorizes organelle contributions into two major areas: host-driven cellular defense mechanisms and pathogen-mediated subversion strategies. Recent work in the field is discussed, providing new insights into host-pathogen dynamics and identifying potential therapeutic targets for improved control of mycobacterial infections.