Mitochondrial plasticity in pathophysiological conditions

Both skeletal and cardiac muscles daily burn tremendous amounts of ATP to meet the energy requirements for contraction. So, it is not surprising that the maintenance of mitochondrial morphology, number, distribution and functionality in striated muscle are important for muscle homeostasis. In these tissues mitochondria present the added dimension of two populations, the intermyofibrillar (IMF) and the subsarcolemmal (SS) mitochondria, being IMF the most abundant one. In the present thesis, the molecular mechanisms harboured in mitochondria of striated muscles were studied using animal models, to better comprehend the role of mitochondrial plasticity in several pathophysiological conditions such as aging, diabetes mellitus and bladder cancer. The comparative analysis of IMF and SS populations isolated from heart evidenced a higher respiratory chain activity of mitochondria interspersed in the contractile apparatus. The higher susceptible of SS respiratory chain complexes subunits to carbonylation, but not to nitration, seems to justify the lower respiratory chain activity observed in this mitochondrial population. Our results showed that in heart from aged mice there is an accumulation of dysfunctional mitochondria. The age-related decrease of oxidative phosphorylation activity seems to be justified, at least partially, by the increased proneness of mitochondrial proteins as OXPHOS subunits and MnSOD to oxidative modifications. Moreover, a sedentary lifestyle seems to worsen the functional consequences of aging in heart by increasing mitochondrial proteins susceptibility to nitration. In skeletal muscle from rats with type 1 diabetes mellitus induced by streptozotocin administration, we verified the accumulation of dysfunctional mitochondria due, at least in part, to the impairment of PQC system. Indeed, the decreased activity of AAA proteases was accompanied by the accumulation of oxidatively modified mitochondrial proteins with impact in respiratory chain activity. The diminishing of mitochondria activity also underlies cancer-induced muscle wasting. Indeed, using a rat model of chemically induced urothelial carcinoma we verified that the loss of gastrocnemius mass was related to mitochondrial dysfunction due to, at least partially, the down-regulation of PQC system involving the mitochondrial proteases paraplegin and Lon. PQC impairment resulted in the accumulation of oxidatively modified mitochondrial proteins. In overall, regardless the pathophysiological stimuli that promote mitochondrial alterations, there are similarities in the pattern of disease-related mitochondrial plasticity. The diminished capacity for ATP production in striated muscle seems to be due to increased oxidative damage of mitochondrial proteins, namely subunits of respiratory chain complexes, metabolic proteins and MnSOD. Our data highlighted, for the first time, the impact of mitochondrial PQC system impairment in the accumulation of oxidized proteins, exacerbating the dysfunction of this organelle in striated muscle in several pathophysiological conditions.

O papel do turismo desportivo no desenvolvimento sustentável das áreas costeiras

Atualmente, a rotina sedentária leva a que as pessoas procurem cada vez mais a prática da atividades diferentes, tais como a atividade desportiva, que se torna essencial como fuga a este estilo de vida. O turismo desportivo tem assim crescido nos últimos anos e, por isso, a oferta existente hoje em dia é bastante variada. No entanto, é necessário ter em atenção que o uso dos recursos naturais, muitas vezes na base destas atividades, não deve ser excessivo. Igualmente, a busca pelo desenvolvimento sustentável deve fazer parte dos planos de todos os intervenientes no desenvolvimento dos destinos turísticos. A presente dissertação foca-se num estudo exploratório, com análise qualitativa, com o objetivo de analisar a importância do turismo desportivo na região de Aveiro. Assim, pretende-se compreender se esta atividade pode contribuir para o desenvolvimento da região de Aveiro enquanto destino turístico, garantindo simultaneamente a sustentabilidade das áreas costeiras. Em concreto, esta investigação realizou-se através de um inquérito por entrevista a agentes de oferta de animação turística que oferecem atividades de turismo desportivo. A necessidade de colaboração com a comunidade local e de integração nesta, bem como a urgência de criar parcerias com empresas do mesmo sector, ou até de sectores diferentes, são dois dos pontos essenciais nesta área, que podem conduzir a um desenvolvimento do turismo desportivo nas áreas costeiras, em concreto na região de Aveiro, sem comprometimento da sustentabilidade local.