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Article
Effects of Local pH on the Formation and Regulation of Cristae Morphologies
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics
  • Dong Hoon Song
  • Jonghyun Park, Missouri University of Science and Technology
  • Martin A. Philbert
  • Ann Marie Sastry
  • Wei Lu
Abstract

Cristae, folded subcompartments of the inner mitochondrial membrane (IMM), have complex and dynamic morphologies. Since cristae are the major site of adenosine triphosphate synthesis, morphological changes of cristae have been studied in relation to functional states of mitochondria. In this sense, investigating the functional and structural significance of cristae may be critical for understanding progressive mitochondrial dysfunction. However, the detailed mechanisms of the formation and regulation of these cristae structures have not been fully elucidated. Among the hypotheses concerning the regulation of cristae morphologies, we exclusively investigate the effects of the local pH gradient on the cristae morphologies by using a numerical model. An area-difference induced curvature of the membrane is modeled as a function of local pH. This curvature is then applied to the finite element model of a closed lipid bilayer in order to find the energetically favorable membrane configuration. From this study, we substantiate the hypothesis that a tubular crista structure can be formed and regulated by the local pH gradient. Through the simulations with various initial conditions, we further demonstrate that the diameter of a crista is mainly determined by the local pH gradient, and the energetically favorable direction of crista growth is perpendicular to the longitudinal axis of a mitochondrion. Finally, the simulation results at the mitochondrial scale suggest that the cristae membrane may have a lower local pH value and/or a higher cardiolipin composition than the other parts of the IMM.

Department(s)
Mechanical and Aerospace Engineering
Comments
This work was supported by National Institutes of Health Grant No. 1R01 ES08846.
Keywords and Phrases
  • Adenosinetriphosphate,
  • Cell membranes,
  • Lipid bilayers,
  • Mitochondria,
  • pH,
  • Phospholipids, Cardiolipins,
  • Functional state,
  • Initial conditions,
  • Inner mitochondrial membranes,
  • Local pH,
  • Longitudinal axis,
  • Mitochondrial dysfunction,
  • Morphological changes, Morphology, lipid bilayer, biological model,
  • computer simulation,
  • finite element analysis,
  • lipid bilayer,
  • metabolism,
  • mitochondrial membrane,
  • pH,
  • ultrastructure, Computer Simulation,
  • Finite Element Analysis,
  • Hydrogen-Ion Concentration,
  • Lipid Bilayers,
  • Mitochondrial Membranes,
  • Models, Biological
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2014 American Physical Society (APS), All rights reserved.
Publication Date
8-1-2014
Publication Date
01 Aug 2014
PubMed ID
25215753
Citation Information
Dong Hoon Song, Jonghyun Park, Martin A. Philbert, Ann Marie Sastry, et al.. "Effects of Local pH on the Formation and Regulation of Cristae Morphologies" Physical Review E - Statistical, Nonlinear, and Soft Matter Physics Vol. 90 Iss. 2 (2014) ISSN: 1539-3755; 1550-2376
Available at: http://works.bepress.com/jonghyun-park/23/