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Mitochondrial Membrane Potential and Dynamics

  • Jorge M. A. OliveiraEmail author
Chapter
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Abstract

Mitochondria are essential for neuronal homeostasis and their dysfunction causes neurodegeneration. Mitochondrial bioenergetics and dynamics ensure ATP supply and Ca2+ buffering throughout neuronal processes, regulating and being reciprocally modulated by synaptic activity. At the core of mitochondrial activity resides the ability to generate a proton motive force, whose major component is the mitochondrial membrane potential (Δψm). This key bioenergetic parameter changes dynamically in living cells in response to metabolic and ionic changes affecting respiratory chain activity. In the absence of dysfunction, transient decreases in Δψm by competing mitochondrial functions (e.g., ATP synthesis or Ca2+ buffering) are readily restored. Even when dysfunctional, mitochondria may maintain Δψm by FoF1-ATPase reversal, thus highlighting the value of dynamic Δψm recordings in response to controlled stimuli. Mitochondrial biogenesis requires Δψm for import of nuclear-encoded proteins. Δψm is necessary for mitochondrial fusion, but not fission. The latter often yields depolarized mitochondria, which when unable to reestablish Δψm are excluded from fusion and likely targeted for autophagy (mitophagy). Mitochondrial dynamic movement and docking are also associated with changes in Δψm, which undergoes local modulation in response to neuronal activity. Mitochondrial diseases may stem from mutations in nuclear or mitochondrial DNA (mtDNA). Mitochondria in neurons with severe mtDNA mutations were shown to hold Δψm by reverse FoF1-ATPase activity, which may theoretically allow complementation by fusion in a heteroplasmic context, and/or allow clonal expansion by preventing exclusion from the fusion pool and mitophagy. In Huntington’s disease and in familial forms of Alzheimer and Parkinson’s diseases, there is mounting evidence for changes in mitochondrial dynamics and Δψm.

Keywords

Membrane potential Dynamics Biogenesis Fusion Fission Trafficking Mitophagy 

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Copyright information

© Springer-Verlag London Limited 2012

Authors and Affiliations

  1. 1.REQUIMTE, Department of Drug Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal

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