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Review
. 2022 Dec 6:10:1082095.
doi: 10.3389/fcell.2022.1082095. eCollection 2022.

Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury

Gaia Pedriali  1 , Daniela Ramaccini  1 , Esmaa Bouhamida  1 , Mariusz R Wieckowski  2 , Carlotta Giorgi  3 , Elena Tremoli  1 , Paolo Pinton  1   3
Affiliations
Review

Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury

Gaia Pedriali et al. Front Cell Dev Biol. .

Abstract

Cardiovascular disease is the most common cause of death worldwide and in particular, ischemic heart disease holds the most considerable position. Even if it has been deeply studied, myocardial ischemia-reperfusion injury (IRI) is still a side-effect of the clinical treatment for several heart diseases: ischemia process itself leads to temporary damage to heart tissue and obviously the recovery of blood flow is promptly required even if it worsens the ischemic injury. There is no doubt that mitochondria play a key role in pathogenesis of IRI: dysfunctions of these important organelles alter cell homeostasis and survival. It has been demonstrated that during IRI the system of mitochondrial quality control undergoes alterations with the disruption of the complex balance between the processes of mitochondrial fusion, fission, biogenesis and mitophagy. The fundamental role of mitochondria is carried out thanks to the finely regulated connection to other organelles such as plasma membrane, endoplasmic reticulum and nucleus, therefore impairments of these inter-organelle communications exacerbate IRI. This review pointed to enhance the importance of the mitochondrial network in the pathogenesis of IRI with the aim to focus on potential mitochondria-targeting therapies as new approach to control heart tissue damage after ischemia and reperfusion process.

Keywords: PTP; cardiac ischemia/reperfusion; mitochondria; mitochondrial biogenesis; mitochondrial dynamics; mitophagy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mitochondria-Plasma membrane communication. Num1/Mdm36 complex anchors the PM to the OMM, with the involvement of cardiolipin. Cardiomyocyte’s T-tubules displays mitochondria-associated caveolae (PM invaginations), which number is increased in response to I/R. Furthermore, the overexpression of Cav-3 showed a cardioprotective effect against I/R.
FIGURE 2
FIGURE 2
Mitochondria-Sarcoplasmic reticulum interaction. This type of interaction forms a region called MAM, fundamental for the presence of several proteins that guarantee a correct tethering and regulate Ca2+ cycle. In general, a reduction in the SR-mitochondria tethering correlates with decrease in mitochondrial Ca2+ uptake, reduction of cell death and cardioprotection to IRI.
FIGURE 3
FIGURE 3
Mitochondria-Nucleus communication. Nucleus control of mitochondrial health is named anterograde signaling, through nuclear genes encoding mitochondrial proteins and via miRNAs. Mitochondria, conversely, use a retrograde signaling induced by Ca2+-dependent stress, mtDNA damage, metabolic disorders and loss of ψm.
FIGURE 4
FIGURE 4
Mitochondrial remodelling and state of health in I/R condition. (A) mPTP involvement in IRI. Schematic representation of the main molecular events involving mPTP in IRI. During ischemia mPTP opening is inhibited, after reperfusion this multiprotein complex opening triggers mitochondrial reactions which lead to cardiomyocytes death. (B). Mitochondrial biogenesis. The biogenic process is activated during ischemia with positive consequences in order to improve cellular metabolism and energy production and to promote cardiac regeneration. (C). Mitochondrial dynamics. Fission process is enhanced during I/R leading to tissue injury. Contrariwise, mitochondrial fusion is reduced and increase of this process showed beneficial effects against IRI. (D). Mitophagic process. Induction of mitophagy during myocardial infarction has cardioprotective effects on the condition that is not a chronic activation, very harmful for cardiac tissue.
FIGURE 5
FIGURE 5
Potential mitochondria-targeting therapied as new approach to control heart tissue damage.
See this image and copyright information in PMC

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References

    1. Abegunde D. O., Mathers C. D., Adam T., Ortegon M., Strong K. (2007). The burden and costs of chronic diseases in low-income and middle-income countries. Lancet 370 (9603), 1929–1938. 10.1016/S0140-6736(07)61696-1 - DOI - PubMed
    1. Adlam V. J., Harrison J. C., Porteous C. M., James A. M., Smith R. A., Murphy M. P., et al. (2005). Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J. 19 (9), 1088–1095. 10.1096/fj.05-3718com - DOI - PubMed
    1. Ahmet I., Tae H. J., Juhaszova M., Riordon D. R., Boheler K. R., Sollott S. J., et al. (2011). A small nonerythropoietic helix B surface peptide based upon erythropoietin structure is cardioprotective against ischemic myocardial damage. Mol. Med. 17 (3-4), 194–200. 10.2119/molmed.2010.00235 - DOI - PMC - PubMed
    1. Alavian K. N., Beutner G., Lazrove E., Sacchetti S., Park H. A., Licznerski P., et al. (2014). An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. U. S. A. 111 (29), 10580–10585. 10.1073/pnas.1401591111 - DOI - PMC - PubMed
    1. Allen M. E., Pennington E. R., Perry J. B., Dadoo S., Makrecka-Kuka M., Dambrova M., et al. (2020). The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats. Commun. Biol. 3 (1), 389. 10.1038/s42003-020-1101-3 - DOI - PMC - PubMed

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