RESUMO
Understanding mitochondrial role in normal physiology and pathological conditions has proven to be of high importance as mitochondrial dysfunction is connected with a number of disorders as well as some of the most common diseases (e.g. diabetes or Parkinson's disease). Modeling mitochondrial dysfunction has been difficult mainly due to unique features of mitochondrial genetics. Here we discuss some of the most important mouse models generated so far and lessons learned from them.
Assuntos
DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/genética , Envelhecimento/genética , Animais , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Proteínas de Grupo de Alta Mobilidade/deficiência , Proteínas de Grupo de Alta Mobilidade/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Doenças Mitocondriais/metabolismo , Mutação , Degeneração Neural/genéticaRESUMO
Mitochondrial dysfunction is heavily implicated in the ageing process. Increasing age in mammals correlates with accumulation of somatic mitochondrial DNA (mtDNA) mutations and decline in respiratory chain function. The age-associated respiratory chain deficiency is typically unevenly distributed and affects only a subset of cells in various human tissues, such as heart, skeletal muscle, colonic crypts and neurons. Studies of mtDNA mutator mice has shown that increased levels of somatic mtDNA mutations directly can cause a variety of ageing phenotypes, such as osteoporosis, hair loss, greying of the hair, weight reduction and decreased fertility. Respiratory-chain-deficient cells are apoptosis prone and increased cell loss is therefore likely an important consequence of age-associated mitochondrial dysfunction. There is a tendency to automatically link mitochondrial dysfunction to increased generation of reactive oxygen species (ROS), however, the experimental support for this concept is rather weak. In fact, respiratory-chain-deficient mice with tissue-specific mtDNA depletion or massive increase of point mutations in mtDNA typically have minor or no increase of oxidative stress. Mitochondrial dysfunction is clearly involved in the human ageing process, but its relative importance for mammalian ageing remains to be established.
Assuntos
Envelhecimento/genética , DNA Mitocondrial/genética , Mitocôndrias/genética , Trifosfato de Adenosina/metabolismo , Animais , Humanos , Camundongos , MutaçãoRESUMO
In this study, we present evidence that red blood cell (RBC) membrane p68 in the Belgrade (b/b) rat is similar if not identical to rat serum albumin (RSA). Structural homology between RSA and the RBC p68 has been determined by a variety of biochemical and immunological criteria. This albumin-like protein is a normal constituent of rat RBC and it is partially exported by exosomes during erythroid differentiation. The endogenous origin of rat RBC albumin-like protein was demonstrated by monitoring protein synthesis in reticulocytes and by identification of reticulocyte mRNA for albumin. Haemolytic anaemia, either hereditary (b/b rat) or drug-induced (phenylhydrazine-treated normal rat), results in increased accumulation of the albumin-like protein in rat RBCs as a result of its induced synthesis.
