Related Experiment Video

Updated: Jun 14, 2025

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
06:07

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

213

Metabolic regulation of the mitochondrial immune checkpoint

David C Montrose1,2, Suchandrima Saha1, Lorenzo Galluzzi3,4,5

  • 1Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.

Oncoimmunology
|August 29, 2024
PubMed

Insights

Depriving colorectal cancer cells of serine disrupts mitochondrial function, leading to immune system activation against tumors. This strategy enhances anticancer immunity by leveraging mitochondrial DNA release and innate immune sensors.

Area of Science:

  • Immunology
  • Cancer Biology
  • Metabolic Therapy

Background:

  • Malignant cells possess unique metabolic vulnerabilities.
  • Mitochondrial dysfunction can be therapeutically induced to elicit anti-tumor responses.
  • Cytosolic DNA sensing pathways, including cGAS-STING, are crucial for innate immunity and cancer surveillance.

Discussion:

  • Serine deprivation impairs mitochondrial function in colorectal cancer cells.
  • This metabolic disruption causes mitochondrial DNA to leak into the cytosol.
  • Leaked mitochondrial DNA triggers the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, activating anti-tumor immunity.

Key Insights:

  • Targeting cellular metabolism, specifically serine synthesis, offers a novel approach to cancer therapy.
  • Inducing mitochondrial dysfunction can reprogram the tumor microenvironment to be immunologically hostile to cancer cells.
  • The cGAS-STING pathway is a critical mediator of the anti-tumor immune response initiated by metabolic stress.

Outlook:

  • Further investigation into serine metabolism and mitochondrial integrity in cancer is warranted.
  • This approach holds potential for combination therapies to enhance existing cancer treatments.
  • Exploring serine deprivation in other cancer types could broaden therapeutic applications.
Keywords:
Apoptotic caspasesBCL2MOMPimmune checkpoint inhibitionsenescencetype I interferon

More Related Videos

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells06:55

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells

Published on: October 19, 2021

3.8K
Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry07:18

Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry

Published on: May 24, 2024

973

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
12.3K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.3K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K