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High-resolution Respirometry to Assess Mitochondrial Function in Permeabilized and Intact Cells
Published on: February 8, 2017
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Cristae remodeling causes acidification detected by integrated graphene sensor during mitochondrial outer membrane
Ted D Pham1, Phi Q Pham2, Jinfeng Li2
1Department of Biomedical Engineering, University of California, Irvine, CA, USA.
Scientific Reports
|October 28, 2016
Summary
Mitochondrial outer membrane permeabilization during apoptosis causes a drop in cytosolic pH. This pH change, linked to proton release from mitochondria, can be reversed by adding cytochrome c.
Area of Science:
- Cell Biology
- Biochemistry
- Nanotechnology
Background:
- The intrinsic apoptotic pathway, involving mitochondrial outer membrane permeabilization (MOMP), is crucial for programmed cell death.
- While BAK/BAX oligomerization, cytochrome c release, and caspase activation are known, the impact of MOMP on cytosolic pH remains unclear.
Purpose of the Study:
- To investigate the effect of mitochondrial outer membrane permeabilization on cytosolic pH.
- To elucidate the mechanisms underlying pH changes during apoptosis.
Main Methods:
- Utilized isolated mitochondria tethered to a graphene-based nanomaterial pH sensor.
- Monitored real-time ionic changes and pH fluctuations during apoptosis induction.
Main Results:
- Mitochondrial outer membrane permeabilization (MOMP) leads to a significant acidification of the surrounding medium.
- Activation of OMA1 protease by BAK conformational changes cleaves OPA1, remodeling cristae and releasing protons.
- The observed drop in extra-mitochondrial pH and membrane potential during apoptosis was reversible upon addition of exogenous cytochrome c.
Conclusions:
- Mitochondrial apoptosis induces a measurable decrease in cytosolic pH due to proton release.
- Graphene-based sensors offer a novel platform for studying mitochondrial dynamics.
- Findings suggest potential for pharmacological targeting of apoptosis-associated pH changes in cancer therapy.
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