Related Experiment Video
Updated: Jan 18, 2026
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Mechanisms and Control of Heme Transport and Incorporation into Cytochrome c
Robert G Kranz1, Molly C Sutherland2
1Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA ;
Insights
New research reveals the structural and mechanistic details of cytochrome c (cyt c) biogenesis pathways. Understanding these pathways, especially in bacteria, offers potential for developing novel antimicrobial strategies by inhibiting cyt c production.
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- Cytochrome c (cyt c) is essential for respiration and photosynthesis, requiring covalently attached heme for function.
- All c-type cytochromes utilize a conserved CXXCH motif for heme attachment.
Purpose of the Study:
- To review recent advances in understanding the three cytochrome c biogenesis pathways (Systems I-III).
- To elucidate the structural and mechanistic basis of these pathways and their potential as antimicrobial targets.
Main Methods:
- Analysis of solved protein structures involved in cyt c biogenesis systems.
- Detailed examination of active sites within cyt c synthases.
- Genomic analyses of bacterial respiratory systems and cytochrome c utilization.
Main Results:
- Structural insights into heme transport, heme binding, and apocytochrome c interaction with synthases.
- Elucidation of chemical mechanisms underlying cyt c biogenesis.
- Identification of evolutionary distinctions between bacterial (Systems I & II) and mitochondrial (System III) pathways.
Conclusions:
- Cytochrome c biogenesis pathways present potential novel antimicrobial targets, particularly due to bacterial pathway distinctiveness.
- Inhibiting cyt c biogenesis could attenuate bacterial growth, offering a new therapeutic avenue.
Abstract:
Cytochrome c (cyt c) is ubiquitous in nature, having evolved billions of years ago to function in respiration and photosynthesis. All c-type cytochromes require covalently attached heme, typically at a CXXCH motif. We highlight new studies from the past five years that address the structural and mechanistic bases for the three cyt c biogenesis pathways (Systems I-III). The solved structures of most of the proteins that comprise these systems provide insights into heme transport, the binding of heme, and the mechanism of apocytochrome c (apocyt c) interaction with the synthases. Detailed analyses of the active sites of each cyt c synthase have elucidated chemical mechanisms underlying cyt c biogenesis and their potential as novel antimicrobial targets. This potential is suggested from an evolutionary perspective, as bacteria use two pathways (Systems I and II) that are structurally and mechanistically distinct from the mitochondrial System III. Genomic analyses of bacteria's respiratory capacity, including their use of c-type cytochromes, reveal how the inhibition of cyt c biogenesis could attenuate growth.
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