ArticleCell2020
Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
117 citing papers in PubMed, 218 citations in OpenAlex.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Cysteine excess triggers a mitochondrial iron-dependent cell death.Nature metabolism · 2026Article
- The high price of 'free' cysteine.Nature metabolism · 2026Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Meloxicam protects against muscle and metabolic decline in ageing through Cdon restoration and oxidative stress modulation.Experimental & molecular medicine · 2026Article
- Amelioration of Fe-Induced NaBiological trace element research · 2026Article
- PRKCD Orchestrates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats by Regulating PINK1/PRKN Mitophagy Pathway.Journal of cellular and molecular medicine · 2026Article
- Fecal calprotectin and gut microbiome in a cohort without intestinal pathologies from northern Italy.iScience · 2026Article
- Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial protein import stress causes lysosomal damage and progressive tissue atrophy.EMBO reports · 2026Article
- Alkaloids from Dendrobium Nobile Lindl Improves Mitochondrial Function by Enhancing the Activity of v-ATPase in APP/PS1 Mice.Neurochemical research · 2026Article
- Vacuolar iron transporters mediate resistance to triadimefon in plant pathogenic fungi.Nature communications · 2026Article
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells.Nature metabolism · 2026Article
- Vacuolar-type HNature communications · 2025Article
- Functional role ofVirulence · 2025Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
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- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintains mitochondrial respiration by spatially compartmentalizing amino acids. Defects in vacuole function result in a breakdown in intracellular amino acid homeostasis, which drives age-related mitochondrial decline. Among amino acids, we find that cysteine is most toxic for mitochondria and show that elevated non-vacuolar cysteine impairs mitochondrial respiration by limiting intracellular iron availability through an oxidant-based mechanism. Cysteine depletion or iron supplementation restores mitochondrial health in vacuole-impaired cells and prevents mitochondrial decline during aging. These results demonstrate that cysteine toxicity is a major driver of age-related mitochondrial deterioration and identify vacuolar amino acid compartmentation as a cellular strategy to minimize amino acid toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.