The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes
Open accessAbstract
Podocyte apoptosis is a potent mechanism of proteinuria in diabetic nephropathy. More detailed mechanistic insight into podocyte apoptosis is needed to better understand the pathogenesis of diabetic nephropathy. An elevated level of serum free fatty acid (FFA), as well as hyperglycemia, is a clinical characteristic in diabetes, although its causal role in podocyte apoptosis remains unclear. This study examined the effect of three types of FFAs, saturated, monounsaturated and polyunsaturated FFAs, on podocyte apoptosis. Palmitate, a saturated FFA, induced endoplasmic reticulum (ER) stress-dependent apoptosis in podocytes. Oleate, a monounsaturated FFA, and eicosapentaenoic acid (EPA), an ω-3 polyunsaturated FFA did not induce apoptosis; rather, they antagonized palmitate-induced apoptosis. Palmitate activated mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a nutrient-sensing kinase regulating a wide range of cell biology. Furthermore, inhibition of mTORC1 activity by rapamycin or siRNA for Raptor, a component of mTORC1, ameliorated palmitate-induced ER stress and apoptosis in podocytes. Activity of mTORC1 is regulated by upstream kinases and Rag/Ragulator-dependent recruitment of mTOR onto lysosomal membranes. Palmitate activated mTORC1 by enhancing recruitment of mTOR onto lysosomal membranes, which was inhibited by co-incubation with oleate or EPA. Inhibition of mTOR translocation onto lysosomes by transfection with dominant-negative forms of Rag ameliorated palmitate-induced apoptosis. This study suggests that saturated and unsaturated FFAs have opposite effects on podocyte apoptosis by regulating mTORC1 activity via its translocation onto lysosomal membranes, and the results provide a better understanding of the pathogenesis in diabetic nephropathy and a novel role of mTORC1 in cell apoptosis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and activates both the NLRP3 inflammasome and mTORC116,17”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [16]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · cited 6×
“mTORC1 is a rapamycinsensitive protein kinase complex of six proteins, including Raptor, that regulates a wide array of cellular processes including cell growth, proliferation and autophagy [19,20].”
InfluentialTOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · cited 2×
“mTORC1 is a rapamycinsensitive protein kinase complex of six proteins, including Raptor, that regulates a wide array of cellular processes including cell growth, proliferation and autophagy [19,20].”
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · cited 1×
“A high glucose condition activates mTORC1 via inhibition of AMP-activated protein kinase (AMPK), an activator of TSC1/2 and a direct suppressor of Raptor [24].”
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · cited 5×
“Contents lists available at ScienceDirect Biochimica et Biophysica Acta j ourna l homepage: www.e lsev ie r .com/ locate /bbad is Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes Mako Yasuda a, Yuki Tanaka a, Shinji Kume a,⁎, Yoshikata Morita a, Masami Chin-Ka…”
InfluentialRoles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,879 · cited 1×
“Palmitate induced phosphorylation of PKR-like kinase (PERK) and overexpression of C/EBP homologous protein (CHOP), a potent proapoptotic transcription factor associated with ER stress [50], in a timedependent manner (Fig.”
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464
Cited by
Sorted by citations
Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy
Tagawa, A., Yasuda, M., Kume, S., Yamahara, K., Nakazawa, J., Chin-Kanasaki, M., Araki, H., Araki, S.-I., Koya, D., Asanuma, K., et al. (2016) · Diabetes · doi:10.2337/db15-0473 · Cited by 315
“Cell Culture The mouse podocyte cell line was cultured as previously described (27,28).”
MethodSelf-citationMann, G., Mora, S., Madu, G., & Adegoke, O. A. J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.702826 · Cited by 283
Linking diet to acne metabolomics, inflammation, and comedogenesis: an update
Melnik, B. (2015) · Clinical, Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s69135 · Cited by 259
“Remarkably, both the NLRP3 inflammasome and mTORC1 are activated by palmitic acid and inhibited by DHA, respectively.(183,208,239) Furthermore, PUFAs counteract the activation of SREBP-1c by increasing SREBP-1c proteolytic cleavage and decreasing its mRNA abundance (Table 2).”
Breaking fat: The regulation and mechanisms of lipophagy
Schulze, R. J., Sathyanarayan, A., & Mashek, D. G. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.06.008 · Cited by 243
“activate and unsaturated FAs inhibit [128,129] - although caution must be noted in interpreting data involving exposure to a high concentration of a single FA as this is unphysiological compared to the diverse mixture of FAs cell are exposed to in vivo.”
Lipids, lysosomes, and autophagy
Jaishy, B. P., & Abel, E. D. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r067520 · Cited by 239
Metadata
- Authors
- Yasuda, M., Tanaka, Y., Kume, S., Morita, Y., Chin-Kanasaki, M., Araki, H., Isshiki, K., Araki, S.-I., Koya, D., Haneda, M., Kashiwagi, A., Maegawa, H., & Uzu, T.
- Affiliations
- Shiga University of Medical Science (JP)
- Kanazawa Medical University (JP)
- Asahikawa Medical University (JP)
- Corresponding author
- Kume, Shinji
- ORCID
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 1842
- Issue
- 7
- Pages
- 1097-1108
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2033453768
- Cited by
- 123
- References
- 57
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 20 · 2020: 16 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 5
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (25713033, 24890089)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- podocyte apoptosis, mTORC1, free fatty acids, palmitate, oleate, eicosapentaenoic acid, endoplasmic reticulum stress, lysosomal translocation, raptors, diabetic nephropathy, proteinuria, saturated fatty acids, omega-3 fatty acids
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cell Line, Diabetic Nephropathies, Fatty Acids, Food, Humans, Lysosomes, Palmitates, Eicosapentaenoic Acid, Apoptosis, Oleic Acid, Multiprotein Complexes, Podocytes, Mice, HEK293 Cells, TOR Serine-Threonine Kinases, Endoplasmic Reticulum Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
