Cited by 150Mitochondrial Function and PathologyATP Synthase and ATPases ResearchCell death mechanisms and regulation

Mitochondrial contact sites: their role in energy metabolism and apoptosis

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Brdiczka, Dieter G., Zorov, Dmitry B., Sheu, Shey-Shing·2006·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

The energy metabolism of the failing heart is characterised by a 30% decrease of the total adenine nucleotides content and what may be more important by a 60% loss of creatine and creatine phosphate [J.S. Ingwall, R.G. Weiss, Is the failing heart energy starved? On using chemical energy to support cardiac function, Circ. Res. 95 (2004) 35-145]. Besides the effect of these changes on the energy supply, failing heart is known to be more vulnerable to Ca2+ overload and apoptosis-inducing processes. Recent studies have pointed to the critical role of mitochondrial contact sites in controlling both the mitochondrial energy metabolism and Ca2+ homeostasis. This review focuses on the structure and function of protein complexes in mitochondrial contact sites and their regulatory role in the cellular bioenergetics, intra- and extra-mitochondrial Ca2+ levels, and release of apoptosis-inducing factors. Firstly, we review the compositions of different contact sites following by the discussion of experimental data obtained with isolated and reconstituted voltage-dependent anion channel-adenine nucleotide translocase complexes and consequences of the complex disassembling. Furthermore, we describe experiments involving the complex-stabilizing conditions in vitro and in intact cells. At the end, we discuss unsolved problems and opportunities for clinical application of the complex-stabilizing factors.

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Crossref · 10.1016/j.bbadis.2005.09.007

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  • VDAC is found at contact sites between the OMM and IMM, where it may complex with energetics-related proteins and apoptotic proteins, and appears to play a central role in facilitating mitochondrial steroidogenic cholesterol transport through interactions with several key proteins.

    “Voltage-dependent anion channel is found at contact sites between the OMM and the IMM (101) where it may complex with energetics-related proteins, such as hexokinase, ANT, and creatine kinase, or with apoptotic proteins of the Bcl-2 family (18), and as noted above, and discussed below in greater detail, appears to play a central role in facilitating mitochondrial steroidogenic cholesterol”

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  1. D. Brdiczka, D.B. Zorov, M.Y. Vyssokikh, The interaction of mitochon- drial creatine kinase with the outer membrane pore (VDAC), and the adenine nucleotide translocator (ANT) has important functions in regulation of energy metabolism and apoptosis, in: C. Vial (Ed.), Creatine Kinase, NovaScience Publisher, New York, 2005.

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Authors
Brdiczka, D. G., Zorov, D. B., & Sheu, S.-S.
Affiliations
  • University of Rochester Medicine (US)
  • Lomonosov Moscow State University (RU)
Corresponding author
Brdiczka, Dieter G.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2006-02
Volume
1762
Issue
2
Pages
148-163
ISSN
0925-4439 (ISSN-L)
OpenAlex
W2114758506
Cited by
150
References
129
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 15 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 9
FWCI
0.65
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association (HL-33333, 0050839T)
  • New York State Department of Health
  • National Institutes of Health (0050839T)
  • National Heart, Lung, and Blood Institute (HL 33333, R01HL033333)
  • National Institute of Neurological Disorders and Stroke (NS-37710, R01NS037710)
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 contact sites, mitochondrial bioenergetics, apoptosis, heart failure, voltage-dependent anion channel, adenine nucleotide translocase, mitochondrial calcium homeostasis, mitochondrial protein complexes, complex stabilization, calcium overload
MeSH terms
Mitochondrial ADP, ATP Translocases, Animals, Energy Metabolism, Mitochondria, Apoptosis, Cytochromes c, Mitochondrial Membranes

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