[Physiopathology of mitochondria. From Luft's disease to aging and diabetes].
The first disease due to disturbances in a cell organelle was discovered in 1959-62, and its basis was loose-coupling of oxidative phosphorylation in the skeletal muscle mitochondria accompanied by severe alterations of their structure (Luft's disease). During the 1980s, functional disturbances and structural alterations in the mitochondria were observed in more than 100 disease entities, mainly in parts of the central nervous system and skeletal muscles. A second breakthrough in this area was the discovery in 1963-64 that mitochondria had their own DNA, mtDNA. Following the observation in 1988 of mutations of mtDNA in mitochondrial diseases, such mutations--mainly deletions and point mutations--were observed in almost all mitochondrial diseases. A remarkable extension of the area is the notion that "normal" ageing is accompanied by decreased oxidative phosphorylation and the appearance of mtDNA mutations. During the last two years, such changes have been demonstrated in diseased states in tissues and organs, which are especially reliant on oxygen supply: in the central nervous system (Parkinson's disease, some types of epilepsy and seizures, Huntington's disease, possibly also in Alzheimer's disease); in heart muscle (cardiomyopathies) and in skeletal muscle. Type 2 diabetes or NIDDM engages two tissues most reliant on oxygen consumption, the pancreatic islets (insulin secretion) and skeletal muscle (insulin sensitivity). Both these functions are genetically determined, the latter to a high degree also controlled by "environmental" factors. The evident age factor in the development of NIDDM could be on a par with the "normal" ageing process.(ABSTRACT TRUNCATED AT 250 WORDS)
Luft
R
R
Rolf Lufts forskningscentrum, Karolinska sjukhuset, Stockholm.
Luthman
H
H
D000375:Aging / Q000502:physiology*; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013577:Syndrome
D004247:DNA
Mitokondriernas patofysiologi. Från Lufts sjukdom till åldrande och diabetes.