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. 2022 Apr 27;23(9):4820. doi: 10.3390/ijms23094820

Figure 1.

Figure 1

Normal mighty mitochondria (Mt). These images demonstrate the normal electron transport chain (ETC) and adenosine triphosphate (ATP) production in a 20-week-old healthy, control C57BL/6J female mouse model. Panel A demonstrates an exploded image of a normal mitochondrion with its numerous cristae (C) (invaginations of the inner membrane to increase its surface area). Note the Krebs—TCA cycle lower-left that utilizes acetyl CoA from either glycolysis or fatty acid metabolism and importantly donates NADH and FADH2 to enter the electron transport chain (ETC) at complex I (CI) in panel B. Additionally, note the folate and methionine cycles representing the Mt folate-mediated one-carbon metabolism (FOCM) with their essential vitamin cofactors B12, B9, and B6. Importantly, formate is supplied to the nucleus via FOCM as well as succinyl-CoA from the methionine cycle (M) and also donates methyl groups to mtDNA, and nuclear DNA for maintenance and repair. Importantly, note that mitochondria have their own circular DNA that is capable of undergoing mutation(s) (Mu). Additionally, note the presence of a mitochondria permeability transition pore (MPTP) lower-right in red coloring. Panel B is an exploded image of the boxed-in (white dashed lines) in panel A, which depicts an even higher exploded magnification (scale bar 100 nm) to improve the clarity of the Mt inner membrane cristae structures and the ETC. Note the movement or flow of electrons (e−) from complex I to complex IV and hydrogen protons (H+), which create the mitochondrial membrane potential (ΔΨm) generated by the proton-pumping action from the matrix to the inner membrane space at complexes I, III, and IV. This results in the formation of ATP (energy) at complex V as protons (H+) flow back into the Mt matrix through complex V resulting in the subsequent formation of ATP (energy) at complex V via the ADP substrate and ATP SYN [8]. The ETC may become overwhelmed when there is nutrient excess, such as occurs in hyperglycemia and hyperlipidemia associated with obesity and T2DM. Additionally, uncoupling protein(s) (UCPs), located on the inner Mt membrane are known to uncouple oxygen consumption by the respiratory chain from ATP synthesis, and it should be noted that thermogenesis (non-shivering) upper-right occurs in brown adipose tissue mitochondria that stain positive for uncoupling protein1 (UCP1) [8]. Original magnification ×12,000 and scale bars = 200 nm (panel A) and 100 nm (panel B). ADP = adenosine diphosphate; ATP SYN = adenosine triphosphate synthase; C = complex; CJ = crista junction; CoA = coenzyme A; FADH2 = reduced flavin adenine dinucleotide; NADH = reduced nicotinamide adenine dinucleotide; OMM = outer mitochondrial membrane; •O2− = superoxide; OXPHOS = oxidative phosphorylation; TCA = tricarboxylic cycle.