title: Mitochondria and energetic depression in cell pathophysiology.
abstract: 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 from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell's ability to do work and control the intracellular Ca(2+) homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with 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.
authors: Department of Pathophysiology, University of Tartu, Tartu, Estonia.
authors: Enn
authors: E
authors: Seppet
authors: Department of Pathophysiology, University of Tartu, Tartu, Estonia.
authors: Marju
authors: M
authors: Gruno
authors: Department of Surgery, University of Tartu, Tartu, Estonia.
authors: Ants
authors: A
authors: Peetsalu
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Zemfira
authors: Z
authors: Gizatullina
authors: Department of Medical Genetics, University of Tübingen, Tübingen, Germany.
authors: Huu Phuc
authors: HP
authors: Nguyen
authors: Department of Neurology, Otto von Guericke University, Magdeburg, Germany.
authors: Stefan
authors: S
authors: Vielhaber
authors: Bernstein Institute for Physiology, Martin-Luther-University Halle-Wittenberg, Germany.
authors: Manfred H P
authors: MHP
authors: Wussling
authors: Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania.
authors: Sonata
authors: S
authors: Trumbeckaite
authors: Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania.
authors: Odeta
authors: O
authors: Arandarcikaite
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Doreen
authors: D
authors: Jerzembeck
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Maria
authors: M
authors: Sonnabend
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Katharina
authors: K
authors: Jegorov
authors: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Germany.
authors: Stephan
authors: S
authors: Zierz
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Frank
authors: F
authors: Striggow
authors: KeyNeurotek AG, ZENIT-Technology Park Magdeburg, Magdeburg, Germany.
authors: Frank N
authors: FN
authors: Gellerich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics*; D006019:Glycolysis / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation
chemical_list: D000255:Adenosine Triphosphate