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Updated: May 28, 2026
09:34
The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells
Published on: July 27, 2018
Modulation of autophagic activity by extracellular pH.
Teng Xu1, Hang Su, Suthakar Ganapathy
1Department of Radiation Oncology, Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Autophagy
|October 15, 2011
Summary
Tumor acidity significantly impacts autophagy, suppressing it in acidic conditions and enhancing it in basic conditions. This pH-dependent autophagy regulation is crucial for understanding cancer progression and developing new therapeutic strategies.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Human cancers often reprogram energy metabolism, shifting from oxidative phosphorylation to aerobic glycolysis.
- This metabolic shift contributes to an acidic tumor microenvironment, often worsened by tumor hypoxia.
- The tumor microenvironment's pH can influence cellular processes like autophagy.
Purpose of the Study:
- To investigate the effect of extracellular pH on autophagic activity in cancer.
- To determine the molecular mechanisms underlying pH-modulated autophagy.
- To explore the implications of pH-dependent autophagy in tumor biology.
Main Methods:
- Culturing cells under varying extracellular pH conditions.
- Measuring autophagic activity using established assays.
- Utilizing gene knockdown of key autophagy-related genes (Beclin 1, Vps34, Atg5).
- Analyzing autophagy in different regions of tumor masses.
Main Results:
- Extracellular pH significantly alters autophagic activity, with opposite effects observed at acidic and basic pH.
- Acidic conditions suppress both basal and starvation-induced autophagy.
- Autophagy suppression in acidic environments requires essential autophagy components like Beclin 1, Vps34, and Atg5.
- Tumor regions with lower extracellular pH exhibit reduced autophagic activity.
Conclusions:
- Extracellular pH is a critical regulator of autophagy in cancer cells.
- Acidic tumor microenvironments inhibit autophagy, potentially impacting cancer cell survival and proliferation.
- Targeting pH-dependent autophagy modulation may offer novel therapeutic strategies for cancer treatment.
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