ArticleThe Journal of biological chemistry2011
Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease.Science (New York, N.Y.) · 2026Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.The Journal of biological chemistry · 2026Article
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Alectinib combined with 5-aminolevulinic acid-based photodynamic therapy promotes apoptosis in endometrial cancer cells by targeting ferrochelatase.Frontiers in oncology · 2026Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025Article
- Lon-dependent proteolysis in oxidative stress responses.Journal of bacteriology · 2025Review
- The mitochondrial LONP1 protease: molecular targets and role in pathophysiology.Molecular biology reports · 2025Review
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- Therapeutic potential of 5-aminolevulinic acid in metabolic disorders: Current insights and future directions.iScience · 2024Review
- Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells.Cell stem cell · 2024Article
- LONP1 alleviates ageing-related renal fibrosis by maintaining mitochondrial homeostasis.Journal of cellular and molecular medicine · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease.Biochemistry · 2024Article
- Multi-modular metabolic engineering of heme synthesis inSynthetic and systems biotechnology · 2024Article
- The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease.Seminars in liver disease · 2023Review
- Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication.Acta pharmaceutica Sinica. B · 2023Article
- The yeast ALA synthase C-terminus positively controls enzyme structure and function.Protein science : a publication of the Protein Society · 2023Article
- LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.EMBO molecular medicine · 2023Article
- Multi-omics analyses reveal ClpP activators disrupt essential mitochondrial pathways in triple-negative breast cancer.Frontiers in pharmacology · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
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Abstract
5-Aminolevulinic acid synthase (ALAS-1) is the first rate controlling enzyme that controls cellular heme biosynthesis. Negative feedback regulation of ALAS-1 by the end product heme is well documented and provides the foundation for heme treatment of acute porphyrias, a group of diseases caused by genetic defects in the heme biosynthesis pathway and exacerbated by controlled up-regulation of ALAS-1. Heme is known to affect ALAS-1 activity by repressing gene transcription, accelerating mRNA degradation, and impeding pre-ALAS-1 mitochondrial translocation. In the current study, we examined the effect of heme on the rate of mature ALAS-1 protein turnover in human cells and tissues and explored the mediator involved in this new regulatory mechanism. We found that heme and other metalloporphyrins such as CoPP and CrPP decreased mitochondrial ALAS-1 protein through proteolysis. This degradative effect cannot be emulated by iron or free protoporphyrin, two major chemical components of the heme ring, and is independent of oxidative stress. Down-regulating the activity of mitochondrial LONP1, an ATP-dependent protease that controls the selective turnover of mitochondrial matrix proteins, with potent inhibitors and specific siRNA diminished the negative effect of heme on mitochondrial ALAS-1. Therefore, our data support the existence of a conserved heme feedback regulatory mechanism that functions on the mature form of ALAS-1 protein through the activity of a mitochondrial proteolytic system.
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