Document Detail


Predicting isoelectric points of nonfunctional mitochondria from Monte Carlo simulations of surface compositions.
MedLine Citation:
PMID:  23294022     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondria are heterogeneous organelles involved in energy production, metabolism, and cellular signaling that oftentimes are isolated from cells for chemical characterization (e.g., proteomic analysis). The chemical composition of the mitochondrial outer membrane is one of the factors defining the mitochondrial isoelectric point (pI), which is a property useful for the analysis and characterization of isolated mitochondria. We previously used capillary isoelectric focusing (cIEF) with laser-induced-fluorescence detection to determine the experimental pI of individual mitochondria after their isolation under depolarizing conditions. This technique revealed that, when kept nonfunctional, mitochondrial pI is heterogeneous as displayed by the observed distributions of pI. To model the effect of surface composition on pI heterogeneity of these mitochondria, we devised a method to predict mitochondrial pI values using simulated surface compositions. The method was initially validated by predicting the pI values of known mitochondrial outer membrane proteins and was then extended to isolated mitochondria, in which both ionizable amino acids and phospholipids contribute to mitochondrial pI. After using a Monte Carlo method to generate a library of over 2 million possible mitochondrial surface compositions, sufficient compositions to match the frequency of occurrence of experimental mitochondrial pI values were randomly selected. This comparison allows for association of a given individual mitochondrial pI with thousands of randomly chosen compositions. The method predicts significant changes in the percentages of some amino acids and phospholipids for observed pI differences between individual mitochondria, which is an important advancement toward explaining the observed heterogeneity of mitochondrial pI.
Authors:
Gregory G Wolken; Benjamin J Fossen; Ayoung Noh; Edgar A Arriaga
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-08
Journal Detail:
Title:  Langmuir : the ACS journal of surfaces and colloids     Volume:  29     ISSN:  1520-5827     ISO Abbreviation:  Langmuir     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-08-13     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  9882736     Medline TA:  Langmuir     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2700-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Isoelectric Point
Mitochondria / chemistry*
Mitochondrial Membranes / chemistry
Models, Molecular
Molecular Dynamics Simulation*
Monte Carlo Method
Surface Properties
Grant Support
ID/Acronym/Agency:
R01 AG020866/AG/NIA NIH HHS; R01-AG020866/AG/NIA NIH HHS; T32 AG029796/AG/NIA NIH HHS; T32-AG029796/AG/NIA NIH HHS
Comments/Corrections

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