Errors, mitochondrial dysfunction and ageing.
Experiments in yeast have shown that increasing the accuracy of mitochondrial ribosomes increases cellular lifespan, which suggests that mitochondrial ribosomal inaccuracy could be a potential source age-related mitochondrial dysfunction. It is argued that experiments used to test the error-catastrophe theory of ageing could therefore be invalid because only proteins synthesized on 80S cytoplasmic ribosomes were analyzed. It is speculated that in elderly mammals, when growth and mitochondrial replacement rates decline, the increased organelle dwell-time allows manifestation of any loss of mito-ribosomal accuracy. The resultant aberrant polypeptides could then overload the Lon protease, which also degrades oxidatively damaged polypeptides, and thereby contribute to the accumulation of damaged macromolecules, mitochondrial dysfunction and senescence. It is suggested that a search for age-related changes in the accuracy of mitochondrial ribosomes be carried out to test the validity or otherwise of these ideas.
Hipkiss
Alan R
AR
Department of Experimental Therapeutics, William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK. alanandjill@lineone.net
D049069:ATP-Dependent Proteases; D000375:Aging / Q000502:physiology*; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000503:physiopathology*; D012270:Ribosomes / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
D006360:Heat-Shock Proteins; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases