Brain Mitochondria: Distribution and Function

ISBN-13: 9781536166507

Silvia Lores-Arnaiz

Opis

"Brain mitochondria: Distribution and Function" offers an overview of significant findings regarding physiological, toxicological and pathological aspects of brain mitochondria properties and their relevant role in cellular bioenergetics. Essential physiological processes such as cell respiration and ATP synthesis, the maintenance of calcium homeostasis, reactive oxygen species generation and apoptotic cell signaling performed by mitochondria are described in the different chapters of this volume. In particular, the importance of specific calcium signaling at synaptic level and its relationship with mitochondrial bioenergetics are extensively described. Being that high energy demands are required at synaptic level for neurotransmission, mitochondrial distribution becomes relevant for essential neuronal processes. Differential bioenergetic characteristics of neuronal, astrocytic and glial mitochondria are discussed. Interestingly, new insights on the interaction between neurotensinergic and nitrergic systems are detailed, based on experimental evidences of the effect of neurotensin receptors blockade on nitric oxide production and mitochondrial function. The chapters describing metal neurotoxicity provide a comprehensive view of the effects of different metals on brain mitochondrial function and their consequences for human health. The impact of iron and copper overload on brain oxidative redox balance and mitochondrial function is fully detailed, focusing on the role of metal-induced neuronal damage on the incidence and progression of neurodegenerative diseases. In addition, a complete revision of the mechanisms underlying heavy metal-mediated damage to brain mitochondria is presented. Neurotoxic effects of arsenic, thallium, lead, cadmium and mercury have been associated with cell bioenergetics impairment, exacerbated production of oxygen free radicals, and induction of intrinsic pathway of apoptosis. Mitochondrial function can also be impaired by treatment with different drugs acting at CNS level. The understanding of the effects of pharmacological agents, abuse drugs, herbicides and insecticides at mitochondrial level can contribute to elucidate the molecular mechanisms involved in neurodegeneration. In this context, the neuroprotective effect of different compounds targeting mitochondrial integrity and function is discussed. Furthermore, mitochondrial alterations, oxygen radicals generation and nitric oxide production are characterized in relation to CNS pathology and hypoxia conditions. Mitochondrial complex I inactivation, oxidative stress and impairment of mitochondrial nitric oxide synthesis are characteristic features of the mitochondrial dysfunction observed in Parkinson's disease and other CNS pathologies. In addition, exposure to hypoxic conditions can affect nitric oxide generation and mitochondrial physiology, with different responses depending on the brain area. As a whole, the understanding of the alterations in mitochondrial distribution and function in the brain associated with neurotoxicity and neurodegeneration may contribute to the knowledge of the role of mitochondria in maintaining the balance between health and disease.