Roles of mitochondria in human disease (original) (raw)

Mitochondria in Health and Diseases

Cells

Mitochondria are subcellular organelles evolved by endosymbiosis of bacteria with eukaryotic cells characteristics. They are the main source of ATP in the cell and play a pivotal role in cell life and cell death. Mitochondria are engaged in the pathogenesis of human diseases and aging directly or indirectly through a broad range of signaling pathways. However, despite an increased interest in mitochondria over the past decades, the mechanisms of mitochondria-mediated cell/organ dysfunction in response to pathological stimuli remain unknown. The Special Issue, “Mitochondria in Health and Diseases,” organized by Cells includes 24 review and original articles that highlight the latest achievements in elucidating the role of mitochondria under physiological (healthy) conditions and, in various cell/animal models of human diseases and, in patients. Altogether, the Special Issue summarizes and discusses different aspects of mitochondrial metabolism and function that open new avenues in un...

Cellular and molecular mechanisms of mitochondrial function

Best Practice & Research Clinical Endocrinology & Metabolism, 2012

Keywords: mitochondria oxidative phosphorylation apoptosis intracellular calcium mitochondrial fission Mitochondria are membrane bound organelles present in almost all eukaryotic cells. Responsible for orchestrating cellular energy production, they are central to the maintenance of life and the gatekeepers of cell death. Thought to have originated from symbiotic ancestors, they carry a residual genome as mtDNA encoding 13 proteins essential for respiratory chain function. Mitochondria comprise an inner and outer membrane that separate and maintain the aqueous regions, the intermembrane space and the matrix. Mitochondria contribute to many processes central to cellular function and dysfunction including calcium signalling, cell growth and differentiation, cell cycle control and cell death. Mitochondrial shape and positioning in cells is crucial and is tightly regulated by processes of fission and fusion, biogenesis and autophagy, ensuring a relatively constant mitochondrial population. Mitochondrial dysfunction is implicated in metabolic and age related disorders, neurodegenerative diseases and ischemic injury in heart and brain.

Mitochondria and Energetic Depression in Cell Pathophysiology

International Journal of Molecular Sciences, 2009

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting OPEN ACCESS activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis.

Mitochondrion: A Common Organelle for Distinct Cell Deaths

Mitochondria are deeply involved in cell fate decisions via their multiple roles in metabolism, cell growth, and cell death. In healthy cells, these functions are highly regulated to provide sufficient energy for cell function, maintain cell homeostasis, and avoid undesirable cell death. This is achieved by an orchestrated cooperation of cellular and molecular mechanisms such as mitochondrial mass control (mitophagy vs biogenesis), oxidative phosphorylation, redox and calcium homeostasis, and the balance between pro-and antiapoptotic proteins. In the 1990s, mitochondria have been demonstrated to

Mitochondrion and its related disorders: Making a comeback

Journal of Zhejiang University-science B, 2008

The great majority of genetic disorders are caused by defects in the nuclear genome. However, some significant diseases are the result of mitochondrial mutations. Because of the unique features of the mitochondria, these diseases display characteristic modes of inheritance and a large degree of phenotypic variability. Recent studies have suggested that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer.

The rise of mitochondria in medicine

Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mito-chondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel mitopathogenic mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article , we overview specific aspects of mitochondrial biology that have contributed to – and likely will continue to enhance the progress of modern medicine.