ArticleMolecular and cellular biology2020
Anabolic SIRT4 Exerts Retrograde Control over TORC1 Signaling by Glutamine Sparing in the Mitochondria.
Article in Molecular and cellular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- SIRT4 positively regulates autophagy via ULK1, but independently of HDAC6 and OPA1.FEBS open bio · 2026Article
- Microglial ER stress response via IRE1α regulates diet-induced metabolic imbalance and obesity in mice.Molecular metabolism · 2025Article
- Diurnal variation in skeletal muscle mitochondrial function dictates time-of-day-dependent exercise capacity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Time Restricted Eating: A Valuable Alternative to Calorie Restriction for Addressing Obesity?Current obesity reports · 2025Review
- Metabolic transitions regulate global protein fatty acylation.The Journal of biological chemistry · 2024Article
- Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses.Frontiers in immunology · 2024Review
- Advances of SIRT4 in cancer metabolism and therapy.Pediatric discovery · 2023Review
- SIRT4 in ageing.Biogerontology · 2023Review
- Sirtuin 4 activates autophagy and inhibits tumorigenesis by upregulating the p53 signaling pathway.Cell death and differentiation · 2023Article
- SIRT4 Expression Ameliorates the Detrimental Effect of Heat Stress via AMPK/mTOR Signaling Pathway in BMECs.International journal of molecular sciences · 2022Article
- Article
- Review
- High glutamine suppresses osteogenesis through mTORC1-mediated inhibition of the mTORC2/AKT-473/RUNX2 axis.Cell death discovery · 2022Article
- Mitochondrial lysine acylation and cardiometabolic stress: Truth or consequence?Current opinion in physiology · 2022Article
- Nuclear-Mitochondrial Interactions.Biomolecules · 2022Review
- Continuous variable responses and signal gating form kinetic bases for pulsatile insulin signaling and emergence of resistance.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Wolbachia and Sirtuin-4 interaction is associated with alterations in host glucose metabolism and bacterial titer.PLoS pathogens · 2020Article
- Metabolic choreography of gene expression: nutrient transactions with the epigenome.Journal of biosciences · 2020Review
- The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Anabolic and catabolic signaling mediated via mTOR and AMPK (AMP-activated kinase) have to be intrinsically coupled to mitochondrial functions for maintaining homeostasis and mitigate cellular/organismal stress. Although glutamine is known to activate mTOR, whether and how differential mitochondrial utilization of glutamine impinges on mTOR signaling has been less explored. Mitochondrial SIRT4, which unlike other sirtuins is induced in a fed state, is known to inhibit catabolic signaling/pathways through the AMPK-PGC1α/SIRT1-peroxisome proliferator-activated receptor α (PPARα) axis and negatively regulate glutamine metabolism via the tricarboxylic acid cycle. However, physiological significance of SIRT4 functions during a fed state is still unknown. Here, we establish SIRT4 as key anabolic factor that activates TORC1 signaling and regulates lipogenesis, autophagy, and cell proliferation. Mechanistically, we demonstrate that the ability of SIRT4 to inhibit anaplerotic conversion of glutamine to α-ketoglutarate potentiates TORC1. Interestingly, we also show that mitochondrial glutamine sparing or utilization is critical for differentially regulating TORC1 under fed and fasted conditions. Moreover, we conclusively show that differential expression of SIRT4 during fed and fasted states is vital for coupling mitochondrial energetics and glutamine utilization with anabolic pathways. These significant findings also illustrate that SIRT4 integrates nutrient inputs with mitochondrial retrograde signals to maintain a balance between anabolic and catabolic pathways.
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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.