Mitochondrial interplay with membrane organelles in health and disease

Mitochondria produce energy by oxidative phosphorylation to support vital physiological processes. In addition to energy production, they are essential for regulating calcium homeostasis, antioxidant defense, lipid metabolism, and programmed cell death pathways, including apoptosis and ferroptosis. Extensive physical and biochemical connections are established between mitochondria and other organelles, including the endoplasmic reticulum (ER), lipid droplets (LDs), lysosomes, peroxisomes, and endosomes. These dynamic inter-organelle interactions facilitate coordinated signaling and material exchange, ultimately shaping cellular metabolism and physiological response. Such functional integration ensures efficient energy distribution and robust quality control mechanisms. Disruptions in these interactions contribute to various pathological conditions, highlighting their biological significance. This review synthesizes the current understanding of mitochondrial crosstalk with membrane organelles, particularly the ER, LDs, lysosomes and endosomes, and explores their implications for health and disease. Deciphering these complex relationships in both physiological and pathological contexts provides mechanistic insights and reveals potential therapeutic strategies.