RNA reports breaking news from mitochondria

Nimesha Tadepalle1, Gerald S Shadel1

  • 1Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.

Molecular Cell
|May 7, 2021
PubMed

Insights

Mitochondrial DNA double-strand breaks trigger a cellular stress response. This study reveals mitochondrial RNA (mtRNA) acts as a retrograde messenger, activating the RIG-I/MAVS innate immune pathway.

Area of Science:

  • Cellular Biology
  • Immunology
  • Genetics

Background:

  • Mitochondrial DNA (mtDNA) integrity is crucial for cellular function.
  • mtDNA damage can induce cellular stress responses.
  • The role of mtDNA damage as a trigger for innate immunity is an emerging area of research.

Purpose of the Study:

  • To investigate the consequences of mitochondrial DNA double-strand (ds) breaks.
  • To identify retrograde signaling molecules involved in mtDNA stress responses.
  • To elucidate the activation of innate immune pathways by mtDNA damage.

Main Methods:

  • Mitochondria-targeted TALENs were used to induce specific mtDNA ds breaks.
  • Ionizing radiation was employed as an additional method to induce mtDNA damage.
  • The RIG-I/MAVS innate immune signaling pathway was analyzed.

Main Results:

  • Mitochondrial RNA (mtRNA) was identified as a retrograde second messenger.
  • mtRNA signaling originates from mtDNA double-strand breaks.
  • Activation of the RIG-I/MAVS innate immune signaling pathway was observed.

Conclusions:

  • mtDNA ds breaks represent a significant form of cellular stress.
  • mtRNA serves as a critical retrograde signal in response to mtDNA stress.
  • mtRNA-mediated signaling activates the RIG-I/MAVS innate immune pathway, linking mtDNA damage to immune responses.

Related Concept Videos

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,...
9.7K
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
17.1K
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
8.4K
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...
4.0K
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,...
14.4K
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
3.8K