Biophysical significance of the inner mitochondrial membrane structure on the electrochemical potential of mitochondria.
The available literature supports the hypothesis that the morphology of the inner mitochondrial membrane is regulated by different energy states, that the three-dimensional morphology of cristae is dynamic, and that both are related to biochemical function. Examination of the correlation between the inner mitochondrial membrane (IMM) structure and mitochondrial energetic function is critical to an understanding of the links between mesoscale morphology and function in progressive mitochondrial dysfunction such as aging, neurodegeneration, and disease. To investigate this relationship, we develop a model to examine the effects of three-dimensional IMM morphology on the electrochemical potential of mitochondria. The two-dimensional axisymmetric finite element method is used to simulate mitochondrial electric potential and proton concentration distribution. This simulation model demonstrates that the proton motive force (Δp) produced on the membranes of cristae can be higher than that on the inner boundary membrane. The model also shows that high proton concentration in cristae can be induced by the morphology-dependent electric potential gradient along the outer side of the IMM. Furthermore, simulation results show that a high Δp is induced by the large surface-to-volume ratio of an individual crista, whereas a high capacity for ATP synthesis can primarily be achieved by increasing the surface area of an individual crista. The mathematical model presented here provides compelling support for the idea that morphology at the mesoscale is a significant driver of mitochondrial function.
Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Dong Hoon
DH
Song
Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Jonghyun
J
Park
Toxicology Program, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
Laura L
LL
Maurer
Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Wei
W
Lu
Toxicology Program, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
Martin A
MA
Philbert
Sakti3, Ann Arbor, Michigan, 48108, USA.
Ann Marie
AM
Sastry
D000255:Adenosine Triphosphate / Q000378:metabolism; D055592:Biophysical Phenomena; D004563:Electrochemistry; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D016012:Poisson Distribution; D013499:Surface Properties; D013816:Thermodynamics
D000255:Adenosine Triphosphate