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Skeletal muscle mitochondrial function in human health and disease


Gehrig, Saskia. Skeletal muscle mitochondrial function in human health and disease. 2016, University of Zurich, Faculty of Science.

Abstract

Mitochondria are unique cell organelles, also called the powerhouses of our cells, which play a central role in human oxygen metabolism and general energy supply. By creating biologically accessible energy, these organelles sustain the maintenance of metabolic function and homeostasis. Therefore, accurate function of mitochondria is crucial to proper skeletal muscle operations as well as to general human health. Already small alterations or defects of mitochondria may have deleterious effects, which could play an important role in the process of aging and in several neuromuscular and neurodegenerative diseases such as Huntington disease, and in particular in mitochondrial cytopathies. Although the importance of proper mitochondrial function for human health and skeletal muscle functioning has been recognized, a comprehensive understanding of the regulations and the underlying mechanisms especially in relation to aging and the development of various neuromuscular diseases is lacking.
Accordingly, the aim of this comprehensive PhD project was to investigate mitochondrial function and its relation to other skeletal muscle properties in healthy young and old individuals and in patients with disorders that may affect skeletal muscle mitochondria such as mitochondrial myopathy and Huntington disease. Therefore, high-resolution respirometry measurements of permeabilized skeletal muscle fibers were conducted. The application of this method thereby allows the preservation of innate mitochondrial function and represents the highest standard approach for the characterisation of mitochondrial function. Regarding mitochondrial characteristics, the three independent studies included in this dissertation revealed the following key findings: 1) Maximal fatty acid oxidative capacity was higher in healthy old compared to fitness-level-matched young individuals, 2) mitochondrial
respiratory capacity of each complex as well as mitochondrial volume density was lower in patients with mitochondrial myopathy and 3) patients with Huntington disease were characterized by lower complex I respiratory and maximal oxidative phosphorylation capacity compared to healthy controls. Consequently, the present findings contribute to the general understanding of mitochondrial characteristics, potential regulatory mechanisms and
adaptations to varying circumstances. Together with previous and future studies these results may potentially lead to the development of effective therapeutic strategies in order to improve mitochondrial function and life quality in aged people as well as in patients with neuromuscular or neurodegenerative diseases.

Abstract

Mitochondria are unique cell organelles, also called the powerhouses of our cells, which play a central role in human oxygen metabolism and general energy supply. By creating biologically accessible energy, these organelles sustain the maintenance of metabolic function and homeostasis. Therefore, accurate function of mitochondria is crucial to proper skeletal muscle operations as well as to general human health. Already small alterations or defects of mitochondria may have deleterious effects, which could play an important role in the process of aging and in several neuromuscular and neurodegenerative diseases such as Huntington disease, and in particular in mitochondrial cytopathies. Although the importance of proper mitochondrial function for human health and skeletal muscle functioning has been recognized, a comprehensive understanding of the regulations and the underlying mechanisms especially in relation to aging and the development of various neuromuscular diseases is lacking.
Accordingly, the aim of this comprehensive PhD project was to investigate mitochondrial function and its relation to other skeletal muscle properties in healthy young and old individuals and in patients with disorders that may affect skeletal muscle mitochondria such as mitochondrial myopathy and Huntington disease. Therefore, high-resolution respirometry measurements of permeabilized skeletal muscle fibers were conducted. The application of this method thereby allows the preservation of innate mitochondrial function and represents the highest standard approach for the characterisation of mitochondrial function. Regarding mitochondrial characteristics, the three independent studies included in this dissertation revealed the following key findings: 1) Maximal fatty acid oxidative capacity was higher in healthy old compared to fitness-level-matched young individuals, 2) mitochondrial
respiratory capacity of each complex as well as mitochondrial volume density was lower in patients with mitochondrial myopathy and 3) patients with Huntington disease were characterized by lower complex I respiratory and maximal oxidative phosphorylation capacity compared to healthy controls. Consequently, the present findings contribute to the general understanding of mitochondrial characteristics, potential regulatory mechanisms and
adaptations to varying circumstances. Together with previous and future studies these results may potentially lead to the development of effective therapeutic strategies in order to improve mitochondrial function and life quality in aged people as well as in patients with neuromuscular or neurodegenerative diseases.

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Additional indexing

Item Type:Dissertation
Referees:Lundby Carsten, Jung Hans H, Flück Martin, Kurtcuoglu Vartan
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2016
Deposited On:29 Feb 2016 15:44
Last Modified:08 Dec 2017 19:11
Number of Pages:102

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