ArticleAutophagy2018
HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- HEPES in Cell Culture Alters the Multi-Omics Profile Exhibited by Gaucher Disease Fibroblasts.Journal of cellular biochemistry · 2026Article
- The influence of cell culture media and their additives on virus inactivation in vitro.GMS hygiene and infection control · 2025Article
- Influx of zwitterionic buffer after intracytoplasmic sperm injection (ICSI) membrane piercing alters the transcriptome of human oocytes.Journal of assisted reproduction and genetics · 2024Article
- Article
- Endoplasmic reticulum stress associated with lead (Pb)-induced olfactory epithelium toxicity in an olfactory dark basal cell line.FEBS open bio · 2023Article
- Glycoprotein Non-Metastatic Protein B (GPNMB): The Missing Link Between Lysosomes and Obesity.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2023Review
- TFEB SUMOylation in macrophages accelerates atherosclerosis by promoting the formation of foam cells through inhibiting lysosomal activity.Cellular and molecular life sciences : CMLS · 2023Article
- Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture.Bioactive materials · 2023Article
- Transcriptional Response in Human Jurkat T Lymphocytes to a near Physiological Hypergravity Environment and to One Common in Routine Cell Culture Protocols.International journal of molecular sciences · 2023Article
- HEPES-buffering of bicarbonate-containing culture medium perturbs lysosomal glucocerebrosidase activity.Journal of cellular biochemistry · 2022Article
- Toward Best Practices for Controlling Mammalian Cell Culture Environments.Frontiers in cell and developmental biology · 2022Review
- Extracellular Acidity Reprograms Macrophage Metabolism and Innate Responsiveness.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Unique Phenotype of Lipid-Laden Macrophages.International journal of molecular sciences · 2021Review
- Lysosomal Biogenesis and Implications for Hydroxychloroquine Disposition.The Journal of pharmacology and experimental therapeutics · 2021Article
- Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.Acta neuropathologica communications · 2020Article
- Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons.AMRC open research · 2020Article
- TFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stress.Theranostics · 2020Article
- Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated. Here, we identify HEPES, a chemical buffering agent that is broadly applied in cell culture, as a potent inducer of lysosome biogenesis. Supplementation of HEPES to cell growth media is sufficient to decouple the MiT/TFE family members-TFEB, TFE3 and MITF-from regulatory mechanisms that control their cytosolic retention. Increased MiT/TFE nuclear import in turn drives the expression of a global network of lysosomal-autophagic and innate host-immune response genes, altering lysosomal dynamics, proteolytic capacity, autophagic flux, and inflammatory signaling. In addition, siRNA-mediated MiT/TFE knockdown effectively blunted HEPES-induced lysosome biogenesis and gene expression profiles. Mechanistically, we show that MiT/TFE activation in response to HEPES requires its macropinocytic ingestion and aberrant lysosomal storage/pH, but is independent of MTORC1 signaling. Altogether, our data underscore the cautionary use of chemical buffering agents in cell culture media due to their potentially confounding effects on experimental results.
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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.