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Cited by 175Mitochondrial Function and PathologyATP Synthase and ATPases ResearchCell death mechanisms and regulation

The reversible Ca2+-induced permeabilization of rat liver mitochondria

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Al-Nasser, I, Crompton, M·1986·Biochemical Journal
DOI 10.1042/bj2390019PMC PMC1147234
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Abstract

Rat liver mitochondria became permeabilized to sucrose according to an apparent first-order process after accumulating 35 nmol of Ca2+/mg of protein in the presence of 2.5 mM-Pi, but not in its absence. A fraction (24-32%) of the internal space remains sucrose-inaccessible. The rate constant for permeabilization to sucrose decreases slightly when the pH is decreased from 7.5 to 6.5, whereas the rate of inner-membrane potential (delta psi) dissipation is markedly increased, which indicates that H+ permeation precedes sucrose permeation. Permeabilization does not release mitochondrial proteins. [14C]Sucrose appears to enter permeabilized mitochondria instantaneously. Chelation of Ca2+ with EGTA restores delta psi and entraps sucrose in the matrix space. With 20 mM-sucrose at the instant of resealing, about 21 nmol of sucrose/mg of protein becomes entrapped. The amount of sucrose entrapped is proportional to the degree of permeabilization. Entrapped sucrose is not removed by dilution of the mitochondrial suspension. Resealed mitochondria washed three times retain about 74% of the entrapped sucrose. In the presence of Ruthenium Red and Ca2+ buffers permeabilized mitochondria reseal only partially with free [Ca2+] greater than 3 microM. [14C]Sucrose enters partially resealed mitochondria continuously with time, despite maintenance of delta psi, in accordance with continued interconversion of permeable and impermeable forms. Kinetic analyses of [14C]sucrose entry indicate two Ca2+-sensitive reactions in permeabilization. This conclusion is supported by the biphasic time courses of resealing and repolarization of permeabilized mitochondria and the acute dependence of the rapid repolarization on the free [Ca2+]. A hypothetical model of permeabilization and resealing is suggested and the potential of the procedure for matrix entrapment of substances is discussed.

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  • MPT is one of the main changes in mitochondria that leads to cell death.

    “The mitochondrial inner membrane permeability transition (MPT) is one of main changes in mitochondria that leads to cell death (Al-Nasser and Crompton, 1986; Hunter and Haworth, 1979).”

    From Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent (2012) · cites this paper as Al-Nasser and Crompton, 1986

    The Introduction (page not available in our copy) links excess mitochondrial Ca2+ to impaired energy production that may ultimately lead to cell death, and describes Ca2+-induced inner-membrane permeabilization. It does not establish that permeability transition itself is a main change leading to cell death; the proposed link is more tentative than the citing sentence suggests. (LLM, conf=0.85)

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  1. Sitaramam, V. & Janardana Sarma, M. K. (1981) Proc. Natl. Acad. Sci. 78, 3441-3445

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Authors
Al-Nasser, I., & Crompton, M.
Affiliations
University College London (GB)
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
1986-10-01
Volume
239
Issue
1
Pages
19-29
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj2390019
PMC
PMC1147234
OpenAlex
W1506478670
Cited by
175
References
26
Citations by year
2026: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2019: 4 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 8 · 2013: 2 · 2012: 6
FWCI
2.59
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
mitochondrial membrane permeabilization, rat liver mitochondria, mitochondrial inner membrane potential, proton permeation, sucrose uptake, calcium buffering, EGTA, ruthenium red, mitochondrial membrane permeability
MeSH terms
Animals, Calcium, Egtazic Acid, Female, Indicators and Reagents, Intracellular Membranes, Membrane Potentials, Mitochondria, Liver, Onium Compounds, Organophosphorus Compounds, Oxidative Phosphorylation, Permeability, Proteins, Rats, Inbred Strains, Sucrose, Rats

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