ArticleNature cell biology2025
ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Enhanced terpenoid synthesis in Alternaria alstroemeriae PPL7 via co-fermentation with Paeonia lactiflora roots: integrated metabolomic and transcriptomic analysis.Archives of microbiology · 2026Article
- Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Epigenome-wide DNA methylation and spontaneous preterm birth among pregnant black women.Clinical epigenetics · 2026Article
- Mechanisms of Metabolic Reprogramming Regulating Immunosuppression in the Gastric Cancer Tumor Microenvironment.Biomolecules · 2026Review
- Immunomodulatory copper-based polyphenol nanozyme for diabetic infectious wound healing via NIR amplified cuproptosis bacteriostat in synergy with ferroptosis inhibition anti-inflammation.Bioactive materials · 2025Article
- The Transgenerational Impact of High-Fat Diet and Diabetic Pregnancy on Embryonic Transcriptomics and Mitochondrial Health.Biomedicines · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
MPC1 and MPC2 are two well-known components of the mitochondrial pyruvate carrier (MPC) complex maintaining MPC activity to transport pyruvate into mitochondria for tricarboxylic acid (TCA) cycle entry in mammalian cells. It is currently unknown whether there is an additional MPC component crucially maintaining MPC complex activity for pyruvate mitochondrial import. Here we show that ALDH4A1, a proline-metabolizing enzyme localized in mitochondria, serves as a previously unrecognized MPC component maintaining pyruvate mitochondrial import and the TCA cycle independently of its enzymatic activity. Loss of ALDH4A1 in mammalian cells impairs pyruvate entry to mitochondria, resulting in defective TCA cycle entry. ALDH4A1 forms an active trimeric complex with MPC1-MPC2 to maintain the integrity and oligomerization of MPC1-MPC2 and facilitates pyruvate transport in an in vitro system. ALDH4A1 displays tumour suppression by maintaining MPC complex activity. Our study identifies ALDH4A1 as an essential component of MPC for pyruvate mitochondrial import, TCA cycle entry and tumour suppression.
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