Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent
Dane M Wolf
Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Graduate Program in Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA
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Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Molecular Biology Institute at UCLA, Los Angeles, CA, USA
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Corresponding Author
Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Molecular Biology Institute at UCLA, Los Angeles, CA, USA
Corresponding Author
Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Graduate Program in Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA
Dane M Wolf
Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Graduate Program in Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA
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Sean T Bailey
Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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David B Shackelford
Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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Orian S Shirihai
Corresponding Author
E-mail address: OShirihai@mednet.ucla.edu
Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Graduate Program in Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA
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*Corresponding author. Tel: +1‐310‐206‐7319; E‐mail: mliesa@mednet.ucla.edu
*Corresponding author. Tel: +1‐617‐230‐8570; E‐mail: OShirihai@mednet.ucla.edu
Abstract
The mitochondrial membrane potential (ΔΨm) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), is considered to carry a uniform ΔΨm. However, sequestration of OXPHOS components in cristae membranes necessitates a re‐examination of the equipotential representation of the IMM. We developed an approach to monitor ΔΨm at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨm, corresponding to cristae and IBM. ΔΨm was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨm heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS‐complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨm. Lastly, we determined that different cristae within the individual mitochondrion can have disparate membrane potentials and that interventions causing acute depolarization may affect some cristae while sparing others. Altogether, our data support a new model in which cristae within the same mitochondrion behave as independent bioenergetic units, preventing the failure of specific cristae from spreading dysfunction to the rest.
