Related Experiment Video

Updated: Jan 11, 2026

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

966

Mitochondrial dysfunction acts as a modulator of the immunometabolic route for activating the cytosolic DNA sensor

Cristina Algieri1, Salvatore Nesci2, Francesca Oppedisano3

  • 1Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Bologna, BO, Italy. cristina.algieri2@unibo.it.

Journal of Translational Medicine
|November 19, 2025
PubMed

Insights

Mitochondrial dysfunction releases mitochondrial DNA (mtDNA), activating innate immunity and altering immune cell metabolism. Understanding this link offers new therapeutic strategies for complex diseases.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Mitochondrial Biology

Background:

  • Mitochondria are key regulators of innate immunity, beyond energy production.
  • Cellular stress can lead to mitochondrial dysfunction and the release of mitochondrial DNA (mtDNA).
  • Released mtDNA acts as a danger signal, activating inflammatory pathways like cGAS-STING, NLRP3, and TLR9.

Purpose of the Study:

  • To review the role of mitochondria as an interface between metabolism and immunity.
  • To explore the mechanisms of mtDNA release and its signaling functions.
  • To discuss the impact of mtDNA release on immune cell metabolism and its translational implications.

Main Methods:

  • Literature review focusing on mitochondrial dysfunction, mtDNA release, and innate immunity.
  • Analysis of molecular mechanisms linking mitochondrial stress to immune activation.
  • Examination of immunometabolic reprogramming driven by mtDNA release.

Main Results:

  • Mitochondrial dysfunction triggers mtDNA release, initiating inflammatory responses.
  • Released mtDNA influences immune cell metabolism, affecting polarization and function.
  • This interplay is implicated in the pathogenesis of neurodegenerative, autoimmune, and neoplastic diseases.

Conclusions:

  • Mitochondria are critical in integrating metabolic and immune signals.
  • mtDNA release is a key event connecting mitochondrial stress to immune activation and metabolic changes.
  • Targeting the mitochondrion-immunity-metabolism axis presents novel therapeutic opportunities for various diseases.
Keywords:
Complex diseasesImmunityInflammationMetabolismMitochondria

More Related Videos

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

1.6K
Immunometabolic Circuits in Infection for Advancing Host Directed Therapies11:12

Immunometabolic Circuits in Infection for Advancing Host Directed Therapies

Published on: September 13, 2024

868

Related Concept Videos

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,...
16.6K
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...
4.6K
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,...
11.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.2K
Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
11.4K