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Assessing mitochondrial dysfunction in cells.

Martin D Brand1, David G Nicholls

  • 1Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. mbrand@buckinstitute.org

The Biochemical Journal
|July 6, 2011
PubMed
Summary
This summary is machine-generated.

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Accurately assessing mitochondrial dysfunction involves defining the specific issue, often focusing on adenosine triphosphate (ATP) production. Measuring metabolic fluxes provides more insight than intermediates, with respiratory control being a key assay for both isolated mitochondria and intact cells.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Mitochondrial dysfunction is a critical factor in various diseases.
  • Assessing mitochondrial function requires a clear definition of the specific dysfunction.
  • Current methods for evaluating mitochondrial dysfunction vary in their experimental control and physiological relevance.

Purpose of the Study:

  • To review and define methods for assessing mitochondrial dysfunction.
  • To highlight the importance of measuring metabolic fluxes for evaluating mitochondrial ATP production.
  • To identify the most informative assays for different experimental systems.

Main Methods:

  • Comparison of flux measurements versus intermediate and potential measurements.
  • Evaluation of mitochondrial respiratory control in isolated mitochondria.

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  • Assessment of cell respiratory control in intact cells, including ATP production and respiratory parameters.

    • Main Results:

    • Flux measurements offer superior insights into ATP production capabilities compared to intermediate or potential measurements.
    • Mitochondrial respiratory control is the optimal assay for isolated mitochondria.
    • Cell respiratory control provides comprehensive data on ATP production, proton leak, coupling efficiency, and respiratory capacity in intact cells.

    Conclusions:

    • Defining the specific aspect of mitochondrial dysfunction is crucial for appropriate assessment.
    • Measuring respiratory control and fluxes provides a more quantitative and informative analysis of mitochondrial function.
    • Combined measurements of respiration and membrane potential enhance the understanding of effector sites and control distribution.