FIG. 1.

Basic mitochondrial structure and function. The figure shows the basic structural components of the five ETC complexes (I, II, III, IV, and V) as well as cytochrome c (Cyc), the flow of electrons through the complexes, and the generation of ATP. Fatty acid oxidation (FAO) and TCA cycle generate NADH and FADH₂ needed to energize mitochondria and establish mitochondrial membrane potential (ΔΨ_m; −180 to −200 mV). ΔΨ_m is also modulated by uncoupling proteins (UCP). Phosphate carriers, including the adenine nucleotide translocase (ANT), regulate mitochondrial matrix phosphate levels. Substrate uptake is mediated through inner mitochondrial membrane (IMM) proteins [e.g., carnitine palmitoyl transferase (CPT) and pyruvate dehydrogenase (PDH)]. Mitochondrial DNA (mtDNA) encodes mitochondrial-specific proteins and cytosolic proteins produced by nuclear DNA (n) are translocated to mitochondria through the translocator of the outer membrane (TOM) and inner mitochondrial membrane (TIM); Ca²⁺ is taken up through the calcium uniporter (CaU). The mitochondrial Ca²⁺ level is dependent on the level of Ca²⁺ within the microdomain with the endoplasmic reticulum (ER). This basic function of mitochondria and its interaction with the nucleus and ER is the basis for understanding the role of the organelle in myriad of mitochondria-related diseases. Reproduced and modified from Wall et al. (604).