Molecular and clinical aspects of mitochondrial diabetes mellitus.
This review provides a compact overview on the contribution of mutations in mtDNA to the pathogenesis of diabetes mellitus, with emphasis on the A3243G mutation in the tRNA(Leu, UUR) gene. This mutation associates in most individuals with maternally inherited diabetes and deafness (MIDD) whereas in some other carriers the MELAS syndrome or a progressive kidney failure is seen. Possible pathogenic mechanisms are discussed especially the question why particular mutations in mtDNA associate with distinct clinical entities. Mutations in mtDNA can affect the ATP production, thereby leading to particular clinical phenotypes such as muscle weakness. On the other hand mtDNA mutations may also alter the intracellular concentration of mitochondrial metabolites which can act as signalling molecules, such as Ca or glutamate. This situation may contribute to the development of particular phenotypes that are associated with distinct mtDNA mutations.
Maassen
J A
JA
Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands. j.a.maassen@lumc.nl
van Essen
E
E
van den Ouweland
J M
JM
Lemkes
H H
HH
D000255:Adenosine Triphosphate / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012356:RNA, Transfer, Leu / Q000235:genetics
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D000255:Adenosine Triphosphate