Cited by 505Cell death mechanisms and regulationMitochondrial Function and PathologyAutophagy in Disease and Therapy

Bcl-xL Prevents Cell Death following Growth Factor Withdrawal by Facilitating Mitochondrial ATP/ADP Exchange

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Heiden, Matthew G.Vander, Chandel, Navdeep S, Schumacker, Paul T, Thompson, Craig B·1999·Molecular Cell

Abstract

Growth factor withdrawal is associated with a metabolic arrest that can result in apoptosis. Cell death is preceded by loss of outer mitochondrial membrane integrity and cytochrome c release. These mitochondrial events appear to follow a relative increase in mitochondrial membrane potential. This change in membrane potential results from the failure of the adenine nucleotide translocator (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP exchange. Bcl-xL expression allows growth factor-deprived cells to maintain sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These data demonstrate that mitochondrial adenylate transport is under active regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand.

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Crossref · 10.1016/s1097-2765(00)80307-x

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Authors
Heiden, M. G. V., Chandel, N. S., Schumacker, P. T., & Thompson, C. B.
Affiliations
  • University of Chicago (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Thompson, Craig B
Venue
Molecular Cell
Publisher
Elsevier BV
Published
1999-02
Volume
3
Issue
2
Pages
159-167
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2010953153
Cited by
505
References
35
Citations by year
2026: 3 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 11 · 2019: 4 · 2018: 11 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 19 · 2013: 11 · 2012: 10
FWCI
19.75
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
Bcl-xL, growth factor withdrawal, apoptosis, adenine nucleotide translocase, voltage-dependent anion channel, mitochondrial membrane potential, cytochrome c release, oxidative phosphorylation, coupled respiration, metabolic arrest
MeSH terms
Adenosine Diphosphate, Sodium-Potassium-Exchanging ATPase, Adenosine Triphosphate, Animals, Biological Transport, Active, Fluorescent Dyes, Gramicidin, Hematopoietic Stem Cells, Interleukin-3, Membrane Potentials, Mitochondria, Oxidative Phosphorylation, Oxygen Consumption, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Apoptosis, Porins, Proto-Oncogene Proteins c-bcl-2, Rhodamine 123, Voltage-Dependent Anion Channels, bcl-X Protein, Mice, Caspase Inhibitors

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