Cited by 59Porphyrin Metabolism and DisordersHemoglobin structure and functionHeme Oxygenase-1 and Carbon Monoxide

The mitochondrial heme metabolon: Insights into the complex(ity) of heme synthesis and distribution

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Piel, Robert B., Dailey, Harry A., Medlock, Amy E.·2019·Molecular Genetics and Metabolism

Abstract

Heme is an essential cofactor in metazoans that is also toxic in its free state. Heme is synthesized by most metazoans and must be delivered to all cellular compartments for incorporation into a variety of hemoproteins. The heme biosynthesis enzymes have been proposed to exist in a metabolon, a protein complex consisting of interacting enzymes in a metabolic pathway. Metabolons enhance the function of enzymatic pathways by creating favorable microenvironments for pathway enzymes and intermediates, facilitating substrate transport, and providing a scaffold for interactions with other pathways, signaling molecules, or organelles. Herein we detail growing evidence for a mitochondrial heme metabolon and discuss its implications for the study of heme biosynthesis and cellular heme homeostasis.

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Crossref · 10.1016/j.ymgme.2019.01.006

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  • Mitochondria regulate key cellular processes including energy production, apoptosis, calcium regulation and thermogenesis.

    “The mitochondrion regulates various biological pathways (for example, cellular energy production, apoptosis, calcium regulation and thermogenesis)”

    From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [6]

    The section ‘The (Mitochondrial) Heme Synthesis Metabolon’ (page unavailable) discusses mitochondrial carbon flux and its interplay with the TCA cycle, while the References (page unavailable) include studies linking mitochondrial membrane changes to apoptosis. These provide limited support for metabolic and apoptotic roles, but the paper does not state the broader claim about energy production or address calcium regulation or thermogenesis. (LLM, conf=0.72)

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Authors
Piel, R. B., Dailey, H. A., & Medlock, A. E.
Affiliations
University of Georgia (US)
Corresponding author
Medlock, Amy E.
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2019-11
Volume
128
Issue
3
Pages
198-203
ISSN
1096-7192 (ISSN-L)
OpenAlex
W2908673125
Cited by
59
References
53
Citations by year
2026: 6 · 2025: 11 · 2024: 5 · 2023: 13 · 2022: 11 · 2021: 9 · 2020: 3 · 2019: 1
FWCI
0.53
Type
journal article
Language
en
Open access
Locations
  • Molecular Genetics and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK096501, DK111653, U54 DK110858)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
heme biosynthesis, heme homeostasis, heme proteins, protein complex formation, enzyme microenvironment, substrate transport, heme toxicity
MeSH terms
Animals, Heme, Homeostasis, Humans, Mitochondria, Mice, Metabolic Networks and Pathways, Metabolome

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