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Mitochondrial disorders are genetic defects of oxidative phosphorylation which can affect different organs or tissues.1 2 These disorders have long been regarded as neuromuscular diseases only,3 but it now appears that they can affect a number of other organs including the heart, liver, pancreas, haematopoietic system, and the kidneys.4 Renal symptoms appear to be more common in children than in adults.
The mitochondrial respiratory chain
Oxidative phosphorylation occurs in the mitochondrial inner membrane and includes the oxidation of fuel molecules by oxygen and the concomitant energy transduction into ATP. During the oxidation process, reducing equivalents are transferred to oxygen through the enzymatic complexes of the mitochondrial respiratory chain: complexes I, III, and IV for NADH producing substrates, complexes II, III, and IV for succinate (fig 1).5 This energy is used by complexes I, III, and IV to pump protons through the mitochondrial inner membrane, which creates a charge differential. The ATP synthase allows protons to flow back into the mitochondrion and uses the released energy for the phosphorylation of ADP to ATP.
The mitochondrial respiratory chain.
The mitochondrial genome
The mitochondrial respiratory chain is a complex metabolic pathway. It is made up of about 100 polypeptides. Most of these are encoded in the nucleus and 13 are encoded in the mitochondria. Mitochondria contain their own DNA. In humans, each mitochondrion contains between two and 10 molecules of mitochondrial DNA (mtDNA), which is a 16.5 kb circular double stranded DNA with two distinct origins of replication. It encodes two ribosomal RNAs, 22 tRNAs, and 13 subunits of the polypeptide enzymes of the respiratory chain: seven subunits for complex I, one subunit for complex III, three subunits for complex IV, and two subunits for complex V.6 The remainder of these complexes, as well as proteins involved in the replication, transcription, and translation of …