ArticleThe EMBO journal2019
A mitochondrial FUNDC1/HSC70 interaction organizes the proteostatic stress response at the risk of cell morbidity.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 111 citations in OpenAlex.
- Error-prone translation as a driver of proteostasis collapse and neurodegeneration.Neural regeneration research · 2026Article
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- Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function.Circulation research · 2026Article
- Mitochondrial proteases maintain cellular protein homeostasis and tissue integrity.Cell & bioscience · 2026Article
- A mitochondria-driven quality control mechanism for peroxisomal membrane proteins.Nature communications · 2026Article
- Synaptic mitochondria in aging and neurodegenerative diseases: Functional decline and vulnerability.Neural regeneration research · 2026Article
- Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.Acta diabetologica · 2026Review
- Mitochondrial AK3 inhibits nuclear β-catenin localization and its activation through enhancing mitochondrial activity.Cell death & disease · 2026Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- The Interaction Between Mitophagy Dysregulation and the Diabetic Bladder Microenvironment.Journal of diabetes · 2026Review
- Endothelial FUNDC1 regulates metabolic reprogramming and the obesity-diabetes transition through the SIRT3/GATA2/endothelin-1 axis.Nature communications · 2026Article
- BCL9 as a Key Player in Wnt/β-catenin Signaling: Implications for Osteogenesis, Tissue Repair, and Oncology.Applied biochemistry and biotechnology · 2026Review
- Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice.Cell death & disease · 2025Article
- DCAF13 influences breast cancer chemotherapy resistance through metabolic reprogramming by regulating c-Myc expression.Medical oncology (Northwood, London, England) · 2025Article
- Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell.Advanced biology · 2025Review
- Mitofusin 2 displays fusion-independent roles in proteostasis surveillance.Nature communications · 2025Article
- The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.Aging and disease · 2024Review
- Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein-Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1).International journal of molecular sciences · 2024Article
- Exercise Alleviates Cardiovascular Diseases by Improving Mitochondrial Homeostasis.Journal of the American Heart Association · 2024Review
17 more citing papers are in PubMed but not listed here.
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15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both protein quality and mitochondrial quality are vital for the cellular activity, and impaired proteostasis and mitochondrial dysfunction are common etiologies of aging and age-related disorders. Here, we report that the mitochondrial outer membrane protein FUNDC1 interacts with the chaperone HSC70 to promote the mitochondrial translocation of unfolded cytosolic proteins for degradation by LONP1 or for formation of non-aggresomal mitochondrion-associated protein aggregates (MAPAs) upon proteasome inhibition in cultured human cells. Integrative approaches including csCLEM, Apex, and biochemical analysis reveal that MAPAs contain ubiquitinated cytosolic proteins, autophagy receptor p62, and mitochondrial proteins. MAPAs are segregated from mitochondria in a FIS1-dependent manner and can subsequently be degraded via autophagy. Although the FUNDC1/HSC70 pathway promotes the degradation of unfolded cytosolic proteins, excessive accumulation of unfolded proteins on the mitochondria prior to MAPA formation impairs mitochondrial integrity and activates AMPK, leading to cellular senescence. We suggest that human mitochondria organize cellular proteostatic response at the risk of their own malfunction and cell lethality.
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