Figures
- Mitochondria

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Figure 1 Human mitochondria. Scanning fluorescence confocal micrograph of a cultured human myoblasts stained with the Mitotracker, which is a fluorescent potentiometric dye taken up specifically by living mitochondria because of their membrane potential. Some mitochondria form discrete organelles (short arrow), but others form a reticulate network (long arrow).

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Figure 2 Schematic diagram of the respiratory chain. Reduced cofactors (NADH and FADH₂) are produced from the intermediary metabolism of carbohydrates, proteins, and fats. These cofactors donate electrons to (e^-) to complex I (NADH-ubiquinone oxidoreductase) and complex II (succinate-ubiquinone oxidoreductase). These electrons flow between the complexes down an electrochemical gradient (black arrow), shuttled by ubiquinone (Q) and cytochrome c (C) involving complex III (ubiquinol-cytochrome c oxidase reductase) and complex IV (cytochrome c oxidase, or COX). Complex IV donates an electron to oxygen which results in the formation of water. Protons (H⁺) are pumped from the mitochondrial matrix into the intermembrane space (red arrows). This proton gradient generates the mitochondrial membrane potential which is harnessed by complex V to synthesise adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi). ANT, adenine nucleotide translocator, which exchanges ADP for ATP across the mitochondrial membrane.

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Figure 3 The human mitochondrial genome. The human mitochondrial genome (mtDNA) is a small 16 569 kb molecule of double stranded DNA. mtDNA encodes for 13 essential components of the respiratory chain. ND1-ND6 and ND4L encode seven subunits of complex I (NADH-ubiquinone oxidoreductase). CYT b is the only mtDNA encoded complex III subunit (ubiquinol-cytochrome c oxidase reductase). COX I to III encode for three of the complex IV (cytochrome c oxidase, or COX) subunits, and the ATP 6 and ATP 8 genes encode for two subunits of complex V (ATP synthase). Two ribosomal RNA genes (12S and 16S rRNA), and 22 transfer RNA genes are interspaced between the protein encoding genes. These provide the necessary RNA components for intramitochondrial protein synthesis. D-loop, the 1.1 kb non-coding region which is involved in the regulation of transcription and replication of the molecule, and is the only region not directly involved in the synthesis of respiratory chain polypeptides; O_H and O_L, the origins of heavy and light strand mtDNA replication.

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Figure 4 Clinical features of mitochondrial disease. Mitochondrial disease may present with single organ involvement (sensorineural deafness, diabetes, visual failure, myopathy, or cardiomyopathy), or multisystem involvement. It may be possible to recognise a specific clinical syndrome (table 2), but often patients do not fit neatly into one particular category. The combination of neurological disease and extraneurological involvement should raise the suspicion of a mitochondrial disorder.