The sensing of mitochondrial DAMPs by non-immune cells

Authors:

Aida Rodríguez-Nuevo1,2,3 and Antonio Zorzano1,2,3
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Affiliations:

1 Institute for Research in Biomedicine (IRB Barcelona). The Barcelona Institute of Science and Technology, Barcelona, Spain.

2 Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, 08028 Barcelona, Spain.

3 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III.

Keywords: 

mitochondria, DAMP, immunity, mitochondrial DNA, TLR9, cGAS.

Abbreviatons:

cGAS – cyclic GMP-AMP synthase,

CL – cardiolipin,

DAMP – damage-associated molecular pattern,

ER – endoplasmic reticulum,

FPR – formyl peptide receptor,

IFN – interferon,

IMM – inner mitochondrial membrane,

MTD – mitochondria-derived DAMP,

mtDNA – mitochondrial DNA,

NFP – N-formyl peptide,

OMM – outer mitochondrial membrane,

PAMP – pathogen-associated molecular pattern,

PRR – Pattern Recognition Receptor,

ROS – reactive oxygen species,

STING - stimulator of interferon genes,

TLR – Toll-like receptor.

Corresponding Author(s):

Antonio Zorzano, Institute for Research in Biomedicine, C/ Baldiri Reixac 10, 08028 Barcelona. Tel:+34-934037197; Fax:+34-934034717 antonio.zorzano@irbbarcelona.org

Conflict of interest statement:

Authors show no conflict of interest in connection with this manuscript.

Please cite this article as:

Aida Rodríguez-Nuevo and Antonio Zorzano (2019). The sensing of mitochondrial DAMPs by non-immune cells. Cell Stress 3(6): 195-207. doi: 10.15698/cst2019.06.190

© 2019 Rodríguez-Nuevo and Zorzano. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and re-production in any medium, provided the original author and source are acknowledged.

Abstract:

Mitochondria are the source of damage-associated molecular patterns (DAMPs), which are molecules that play a key modulatory role in immune cells. These molecules include proteins and peptides, such as N-formyl peptides and TFAM, as well as lipids, and metabolites such as cardiolipin, succinate and ATP, and also mitochondrial DNA (mtDNA). Recent data indicate that somatic cells sense mitochondrial DAMPs and trigger protective mechanisms in response to these signals. In this review we focus on the well-described effects of mitochondrial DAMPs on immune cells and also how these molecules induce immunogenic responses in non-immune cells. Special attention will be paid to the response to mtDNA.