Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function

Immune cell function crucially depends on mitochondrial bioenergetics. Mitochondrial function is controlled by their dynamics where coordinated forces of fission and fusion shape mitochondrial morphologies. Genetic deletion of fission and fusion proteins impacts on immune cell metabolism and function. The regulatory network of mitochondrial fusion/fusion responds rapidly to metabolic cues, supporting reciprocal crosstalk between mitochondrial dynamics and immunometabolism. Given the additional non-mitochondrial functions of the fission/fusion machinery, and the formation of functional interactions between mitochondria and other organelles, experimental data on mitochondrial dynamics require careful interpretation. Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism. Metabolic cues can control the mitochondrial fission and fusion machinery to acquire specific morphologies that shape their activity. We review the dynamic properties of mitochondria and discuss how these organelles interlace with immune cell metabolism and function. Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism. Metabolic cues can control the mitochondrial fission and fusion machinery to acquire specific morphologies that shape their activity. We review the dynamic properties of mitochondria and discuss how these organelles interlace with immune cell metabolism and function. programmed cell death. a process that depends on the de novo formation of a double-membrane enclosed organelle, the autophagosome, that is able to engulf cytosolic material and target it for lysosomal degradation. the folds of the inner mitochondrial membrane. at the inner mitochondrial membrane (IMM) four complexes (I–IV) transfer electrons from electron donors to acceptors to produce an electrochemical proton gradient across the IMM. a single-membrane enclosed organelle important for protein secretion, calcium homeostasis, and lipid metabolism. a monolayer-confined organelle functioning as a storage site for intracellular fatty acids and cholesterol. a single-membrane enclosed acidic organelle that drives the degradation of proteins, lipids, and carbohydrates in a pH-dependent manner. circular DNA localized in the mitochondrial matrix, encoding 37 mitochondrial genes, including two rRNAs, 22 tRNAs, and 13 polypeptides. as a result of ETC leakage, electrons are transferred to oxygen, producing superoxides and eventually hydrogen peroxide. a conserved stress program involved in mitochondrial chaperone and protease gene expression, metabolic adaptation, and immune responses. the autophagosomal removal of damaged mitochondria. Several pathways exist, the most prominent being driven by Pink1/parkin. Loss of mitochondrial membrane potential induces Pink1 stabilization on the OMM and recruitment of the E3 ligase parkin, marking mitochondria as autophagosomal targets. at the inner mitochondrial membrane four complexes (I–IV) transfer electrons from electron donors to acceptors to produce an electrochemical proton gradient across the IMM. This is used by the ATP synthase (complex V) to synthesize ATP from ADP and inorganic phosphate. a single-membrane enclosed organelle driving non-mitochondrial fatty acid oxidation, lipid synthesis, and ROS production. superoxides and hydrogen peroxide that are produced from different cellular sources. the difference between OXPHOS at basal and at maximal activity. supramolecular structures comprising OXPHOS enzymes in the IMM. the stepwise oxidation of acetyl-CoA in the mitochondrial matrix, generating reducing equivalents NADH and FADH2. the equivalent of the lysosome in Saccharomyces cerevisiae.