Koopman 2014 Abstract MiP2014
|Redox regulation of mitochondrial dynamics and function.|
Within living cells, individual mitochondria are motile and continuously divide and fuse (mitochondrial dynamics). It appears that these processes allow dissipation of metabolic energy, complementation of mtDNA mutations, separation of mitochondrial content between daughter cells, apoptosis induction and turnover of damaged organelles by mitophagy. Between different cell types and experimental conditions mitochondria display a large variety of shapes. These range between “giant” spherical and “hyperfused” tubular morphologies. The various structural phenotypes likely represent different metabolic states and are important for mitochondrial adaptation to metabolic stress. Interestingly, evidence was provided that changes in mitochondrial volume and (ultra)structure directly affect the properties of (diffusion-limited) biochemical reactions within the mitochondrial matrix. This might allow cells to control the dynamics of biochemical reactions in this compartment by modifying its nanostructure. During both normal and pathological conditions mitochondria and other cellular constituents generate reactive oxygen species (ROS) which can act as signaling and/or damaging molecules. Accumulating evidence suggests a mechanistic link between cellular and mitochondrial ROS signals and mitochondrial (ultra)structure and motility. The fact that mitochondria can be important sources of cellular ROS, especially under pathophysiological conditions, opens the intriguing possibility that mitochondrial ROS could act as autoregulatory factors of mitochondrial (and thereby cellular) function and metabolism.
Labels: MiParea: mt-Structure;fission;fusion, mtDNA;mt-genetics
Event: A2, Oral MiP2014
1-Dep Biochem, Radboud Inst Mol Life Sc, Radboud Univ Medical Center, Nijmegen, The Netherlands; 2-Univ Bordeaux, Maladies Rares: Génétique Métabolisme, France; 3-Dep Cell Biol, Radboud Inst Molecular Life Sc, Radboud Univ Medical Center, Nijmegen, The Netherlands; 4-MRC Mitochondrial Biol Unit, Cambridge, United Kingdom. – [email protected]
References and acknowledgements
Supported by: the “Centres for Systems Biology Research initiative” (CSBR09/013V) of NWO (The Netherlands Organisation for Scientific Research).
- Bénard G, Massa F, Puente N, Lourenço J, Bellocchio L, Soria-Gómez E, Matias I, Delamarre A, Metna-Laurent M, Cannich A, Hebert-Chatelain E, Mulle C, Ortega-Gutiérrez S, Martín-Fontecha M, Klugmann M, Guggenhuber S, Lutz B, Gertsch J, Chaouloff F, López-Rodríguez ML, Grandes P, Rossignol R, Marsicano G (2012) Mitochondrial CB₁ receptors regulate neuronal energy metabolism. Nat Neurosci 15:558-64.
- Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cochemé HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP (2013) Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial Complex I. Nat Med 19:753-9.
- Dieteren CE, Gielen SC, Nijtmans LG, Smeitink JA, Swarts HG, Brock R, Willems PH, Koopman WJ (2011) Solute diffusion is hindered in the mitochondrial matrix. Proc Natl Acad Sci USA 108:8657-62.
- Distelmaier F, et al (2012) Trolox-sensitive ROS regulate mitochondrial morphology, oxidative phosphorylation and cytosolic calcium handling in healthy cells. Antioxidants Redox Signaling 17:1657-69.
- Koopman WJH, et al (2012) Monogenic mitochondrial disorders. N Eng J Med 366:1132-41.
- Koopman WJH, et al (2013) OXPHOS mutations and neurodegeneration. EMBO J 32:9-29.
- Melser S, et al (2013) Rheb regulates mitophagy induced by mitochondrial energetic status. Cell Metab 17:719-30.
- Murphy MP (2013) Mitochondrial dysfunction indirectly elevates ROS production by the endoplasmic reticulum. Cell Metab 18:145-6.
- Willems PH et al (2013) BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion. Antioxidants Redox Signaling 18:129-38.