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Cited by 522Cell death mechanisms and regulationMitochondrial Function and PathologyAutophagy in Disease and Therapy

The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis

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Hüttemann, Maik, Pecina, Petr, Rainbolt, Matthew, Sanderson, Thomas H., Kagan, Valerian E., Samavati, Lobelia, Doan, Jeffrey W., Lee, Icksoo·2011·Mitochondrion
DOI 10.1016/j.mito.2011.01.010PMC PMC3075374
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Abstract

Cytochrome c (Cytc) is essential in mitochondrial electron transport and intrinsic type II apoptosis. Mammalian Cytc also scavenges reactive oxygen species (ROS) under healthy conditions, produces ROS with the co-factor p66(Shc), and oxidizes cardiolipin during apoptosis. The recent finding that Cytc is phosphorylated in vivo underpins a model for the pivotal role of Cytc regulation in making life and death decisions. An apoptotic sequence of events is proposed involving changes in Cytc phosphorylation, increased ROS via increased mitochondrial membrane potentials or the p66(Shc) pathway, and oxidation of cardiolipin by Cytc followed by its release from the mitochondria. Cytc regulation in respiration and cell death is discussed in a human disease context including neurodegenerative and cardiovascular diseases, cancer, and sepsis.

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Cited by

Sorted by citations

Authors
Hüttemann, M., Pecina, P., Rainbolt, M., Sanderson, T. H., Kagan, V. E., Samavati, L., Doan, J. W., & Lee, I.
Affiliations
  • Wayne State University (US)
  • University of Pittsburgh (US)
Corresponding author
Hüttemann, Maik
ORCID
Venue
Mitochondrion
Publisher
Elsevier BV
Published
2011-05
Volume
11
Issue
3
Pages
369-381
ISSN
1567-7249 (ISSN-L)
DOI
10.1016/j.mito.2011.01.010
PMC
PMC3075374
OpenAlex
W1963907102
Cited by
522
References
9
Citations by year
2026: 23 · 2025: 32 · 2024: 40 · 2023: 35 · 2022: 30 · 2021: 46 · 2020: 40 · 2019: 47 · 2018: 36 · 2017: 31 · 2016: 29 · 2015: 36 · 2014: 22 · 2013: 34 · 2012: 29
FWCI
2.79
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Mitochondrion (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (GM089900, HL70755, HL094488, U19A1068021, OH008282)
  • Center for Molecular Medicine and Genetics
  • Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit
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
cytochrome c, apoptosis, mitochondrial electron transport chain, reactive oxygen species, p66Shc, cardiolipin oxidation, mitochondrial membrane potential, mitochondrial release, cell death regulation, neurodegenerative diseases, cardiovascular disease, cancer, sepsis
MeSH terms
Eukaryotic Cells, Gene Expression Regulation, Humans, Apoptosis, Cell Respiration, Mitochondrial Diseases, Cytochromes c

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