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. 2012:2012:329635.
doi: 10.1155/2012/329635. Epub 2011 Nov 14.

Mitochondria-ros crosstalk in the control of cell death and aging

Saverio Marchi  1 , Carlotta Giorgi, Jan M Suski, Chiara Agnoletto, Angela Bononi, Massimo Bonora, Elena De Marchi, Sonia Missiroli, Simone Patergnani, Federica Poletti, Alessandro Rimessi, Jerzy Duszynski, Mariusz R Wieckowski, Paolo Pinton
Affiliations

Mitochondria-ros crosstalk in the control of cell death and aging

Saverio Marchi et al. J Signal Transduct. 2012.

Abstract

Reactive oxygen species (ROS) are highly reactive molecules, mainly generated inside mitochondria that can oxidize DNA, proteins, and lipids. At physiological levels, ROS function as "redox messengers" in intracellular signalling and regulation, whereas excess ROS induce cell death by promoting the intrinsic apoptotic pathway. Recent work has pointed to a further role of ROS in activation of autophagy and their importance in the regulation of aging. This review will focus on mitochondria as producers and targets of ROS and will summarize different proteins that modulate the redox state of the cell. Moreover, the involvement of ROS and mitochondria in different molecular pathways controlling lifespan will be reported, pointing out the role of ROS as a "balance of power," directing the cell towards life or death.

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Figures

Figure 1
Figure 1
Mitochondrial sources of ROS and mitochondrial ROS targets. ROS generators (red) and ROS targets (yellow) are shown in their precise localizations inside mitochondria. Dotted yellow trace encloses the permeability transition pore components. See text, in particular sections 2 and 3, for further details. Abbreviations: OMM: outer mitochondrial membrane; IMS: intermembrane space; IMM: inner mitochondrial membrane; MAO A/B: monoamine oxidases A and B; Cyt. b5 reduct.: cytochrome b5 reductase; DHOH: dihydroorotate dehydrogenase; mGPDH: glycerol-3-phosphate dehydrogenase; I, II, III, and IV: Complex I to IV of the respiratory chain; Q: coenzyme Q; Cyt. c: cytochrome c; KGDHC: α-ketoglutarate dehydrogenase complex; PGDH: pyruvate dehydrogenase complex; e−: electrons; VDAC, voltage-dependent anion channel, Cycl. D: cyclophilin D; ANT: adenine nucleotide translocase; Pol. Γ: polymerase γ; mtDNA: mitochondrial DNA.
Figure 2
Figure 2
ROS levels control cell fate. Low production of ROS works as trigger of autophagic/mitophagic process, with consequent removal of damaged mitochondria and in turn cellular survival (upper panel). On the other hand, high levels of ROS lead to cell death promoting the apoptotic pathway when prosurvival attempt fails (lower panel).
See this image and copyright information in PMC

References

    1. Palade GE. An electron microscope study of the mitochondrial structure. Journal of Histochemistry and Cytochemistry. 1953;1(4):188–211. - PubMed
    1. Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nature Reviews Drug Discovery. 2010;9(6):447–464. - PubMed
    1. Jezek P, Hlavata L. Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. International Journal of Biochemistry & Cell Biology. 2005;37(12):2478–2503. - PubMed
    1. Muller FL, Liu Y, van Remmen H. Complex III releases superoxide to both sides of the inner mitochondrial membrane. Journal of Biological Chemistry. 2004;279(47):49064–49073. - PubMed
    1. Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochemical Journal. 1992;284(1):1–13. - PMC - PubMed

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