Topics in current genetics ; Vol. 8
[1st ed.] XVI, 333 s. : il.
- MeSH
- Cytochromes c physiology MeSH
- Oxygen metabolism MeSH
- Mitochondria enzymology MeSH
- Protons MeSH
- Electron Transport Complex IV analysis physiology chemistry MeSH
- Electron Transport genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Review MeSH
International review of neurobiology ; Vol. 53
[1st ed.] 559 s. : il.
Acta Universitatis upsaliensis. Comprehensive summaries of Uppsala dissertations from the Faculty of Medicine, ISSN 0282-7476 No. 765
49 s. ; 24 cm
Medical Intelligence Unit
[1st ed.] 412 s.
Ochorenia s postihnutím nervového systému spôsobeným poruchou funkcie mitochondrií zahŕňajú pestrú paletu typov dedičnosti, poškodenia jednotlivých častí nervového systému v kombinácii s prejavmi dysfunkcie iných systémov s vysokými nárokmi na energetické zásobenie. Prístup k členeniu mitochondriálnych ochorení môže vychádzať primárne z klinického obrazu, z typu biochemického poškodenia alebo typu genetického poškodenia. V našej práci opisujeme syndrómové mitochondriálne ochorenia – ochorenia, ktorých fenotypická prezentácia tvorí ucelený syndróm. Diagnostika týchto ochorení, okrem zohľadnenia anamnézy a klinického obrazu, spočíva jednak v genetickom objasnení prítomného defektu, jednak v zistení zmien na mikroskopickej a biochemickej úrovni. V súčasnosti nie je v drvivej väčšine týchto ochorení možná účinná kauzálna liečba. Ich správna diagnostika však dáva predpoklad na uplatnenie účinnej liečby, ktorej perspektíva sa črtá v blízkej budúcnosti.
Diseases with nervous system involvement caused by impaired mitochondrial function include a wide range of types of inheritance, damage to individual parts of the nervous system in combination with manifestations of dysfunction of other systems with high demands for energy supply. The approach to classifying mitochondrial disease can be primarily based on the clinical presentation, the type of biochemical damage, or the type of genetic damage. The paper describes mitochondrial disease syndromes, i.e. diseases whose phenotypic presentation forms a coherent syndrome. Diagnosing these diseases, in addition to taking into account the history and clinical presentation, involves genetic elucidation of the present defect as well as identification of changes at a microscopic and biochemical level. Currently, no effective causal therapy is available in the vast majority of these conditions. Correct diagnosis, however, creates the precondition for the use of effective treatment the perspective of which is in sight in the near future.
- MeSH
- Acidosis, Lactic diagnosis physiopathology MeSH
- Diagnostic Techniques and Procedures MeSH
- Friedreich Ataxia physiopathology MeSH
- Kearns-Sayre Syndrome physiopathology MeSH
- Optic Atrophy, Hereditary, Leber physiopathology MeSH
- Leigh Disease physiopathology MeSH
- Humans MeSH
- Brain Diseases, Metabolic, Inborn * diagnosis metabolism physiopathology MeSH
- DNA, Mitochondrial genetics MeSH
- Mitochondrial Encephalomyopathies * diagnosis physiopathology therapy MeSH
- Mitochondrial Diseases * diagnosis physiopathology therapy MeSH
- Mitochondria genetics metabolism MeSH
- Brain metabolism physiopathology MeSH
- Spinal Cord Diseases diagnosis metabolism physiopathology MeSH
- Diffuse Cerebral Sclerosis of Schilder physiopathology MeSH
- MELAS Syndrome diagnosis physiopathology MeSH
- MERRF Syndrome diagnosis physiopathology MeSH
- Check Tag
- Humans MeSH
We report that tumor cells without mitochondrial DNA (mtDNA) show delayed tumor growth, and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory (super)complexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest pathophysiological processes for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.
- MeSH
- Citrate (si)-Synthase metabolism MeSH
- Electron Transport Chain Complex Proteins metabolism MeSH
- Energy Metabolism MeSH
- Transplantation, Homologous MeSH
- Melanoma, Experimental pathology MeSH
- RNA, Messenger metabolism MeSH
- DNA, Mitochondrial metabolism MeSH
- Mitochondria genetics metabolism ultrastructure MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C57BL MeSH
- Mice, Inbred NOD MeSH
- Mice, SCID MeSH
- Mice MeSH
- NADH Dehydrogenase genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Lung Neoplasms pathology secondary MeSH
- Cell Proliferation MeSH
- Reactive Oxygen Species metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Mitochondria are organelles present in most eukaryotic cells, where they play major and multifaceted roles. The classical notion of the main mitochondrial function as the powerhouse of the cell per se has been complemented by recent discoveries pointing to mitochondria as organelles affecting a number of other auxiliary processes. They go beyond the classical energy provision via acting as a relay point of many catabolic and anabolic processes, to signaling pathways critically affecting cell growth by their implication in de novo pyrimidine synthesis. These additional roles further underscore the importance of mitochondrial homeostasis in various tissues, where its deregulation promotes a number of pathologies. While it has long been known that mitochondria can move within a cell to sites where they are needed, recent research has uncovered that mitochondria can also move between cells. While this intriguing field of research is only emerging, it is clear that mobilization of mitochondria requires a complex apparatus that critically involves mitochondrial proteins of the Miro family, whose role goes beyond the mitochondrial transfer, as will be covered in this review.
- MeSH
- Biological Transport, Active physiology MeSH
- Humans MeSH
- Mitochondrial Proteins genetics metabolism MeSH
- Mitochondria genetics metabolism MeSH
- Pyrimidines biosynthesis MeSH
- rho GTP-Binding Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Video-Audio Media MeSH
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- MeSH
- Amides chemistry immunology MeSH
- Antifungal Agents chemistry immunology MeSH
- Chloramphenicol chemistry immunology MeSH
- Peptides, Cyclic chemistry immunology MeSH
- Research Support as Topic MeSH
- Caffeine chemistry immunology MeSH
- Yeasts drug effects MeSH
- DNA, Mitochondrial drug effects MeSH
- Mitochondria physiology drug effects MeSH
- Saccharomyces cerevisiae drug effects MeSH
OBJECTIVE: The present study evaluated the association of psychological distress and radiation exposure as a work-related stressor with mitochondrial function in health care professionals. METHODS: Health care professionals at a regional hospital in Italy were evaluated for physical health and psychological measures using self-report questionnaires (n = 41; mean age = 47.6 [13.1] years; 66% women). In a second sample, individuals exposed to elevated levels of ionizing radiation (IR; likely effective dose exceeding 6 mSv/y; n = 63, mean age = 45.8 [8.8] years; 62% women) were compared with health care workers with low IR (n = 57; mean age = 47.2 [9.5] years; 65% women) because exposure to a toxic agent might act as a (work-related) stressor. Associations were examined between psychological factors (12-item General Health Questionnaire, Perceived Stress Scale), work ability (Work Ability Index), and IR exposure at the workplace with markers of mitochondrial function, including mitochondrial redox activity, mitochondrial membrane potential, mitochondrial DNA (mtDNA) copy number, biogenesis, and mtDNA damage response measured from peripheral blood mononuclear cells. RESULTS: All participants were in good physical health. Individuals reporting high levels of psychological distress showed lower mitochondrial biogenesis as indicated by peroxisome proliferator-activated receptor-γ coactivator 1-α and lower nuclear factor erythroid 2-related factor 2 (NRF2) expression (2.5 [1.0] versus 1.0 [0.9] relative expression [rel exp], p = .035, and 31.5 [5.0] versus 19.4 [6.9] rel exp, p = .013, respectively). However, exposure to toxic agents (IR) was primarily associated with mitochondrial metabolism and reduced mtDNA integrity. Participants with IR exposure displayed higher mitochondrial redox activity (4480 [1202] mean fluorescence intensity [MFI]/min versus 3376 [983] MFI/min, p < .001) and lower mitochondrial membrane potential (0.89 [0.09] MFI versus 0.95 [0.11] MFI, p = .001), and reduced mtDNA integrity (1.18 [0.21] rel exp versus 3.48 [1.57] rel exp, p < .001) compared with nonexposed individuals. CONCLUSIONS: This study supports the notion that psychological distress and potential stressors related to toxic agents might influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria.
