TY - JOUR
T1 - Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases
AU - Giorgi, Carlotta
AU - Marchi, Saverio
AU - Simoes, Ines C.M.
AU - Ren, Ziyu
AU - Morciano, Giampaolo
AU - Perrone, Mariasole
AU - Patalas-Krawczyk, Paulina
AU - Borchard, Sabine
AU - Jędrak, Paulina
AU - Pierzynowska, Karolina
AU - Szymański, Jędrzej
AU - Wang, David Q.
AU - Portincasa, Piero
AU - Węgrzyn, Grzegorz
AU - Zischka, Hans
AU - Dobrzyn, Pawel
AU - Bonora, Massimo
AU - Duszynski, Jerzy
AU - Rimessi, Alessandro
AU - Karkucinska-Wieckowska, Agnieszka
AU - Dobrzyn, Agnieszka
AU - Szabadkai, Gyorgy
AU - Zavan, Barbara
AU - Oliveira, Paulo J.
AU - Sardao, Vilma A.
AU - Pinton, Paolo
AU - Wieckowski, Mariusz R.
N1 - Funding Information:
CG is supported by local funds from the University of Ferrara, the Italian Association for Cancer Research (AIRC: IG-19803), the Italian Ministry of Health, and by a Fondazione Cariplo grant. I.C.M.S, H.Z., P.J.O., V.S, P.P and M.R.W. gratefully acknowledge the financial support for this research from the FOIE GRAS and mtFOIE GRAS projects. These projects received funding from the European Union's Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 722619 (FOIE GRAS) and Grant Agreement No. 734719 (mtFOIE GRAS). This research was also supported by the Polish National Science Centre grants (UMO-2014/15/B/NZ1/00490) for M.R.W., (UMO-2013/08/W/NZ1/00687) for J.D., J.S. and P.P.K., (2015/17/N/NZ2/04267) for P.J. and G.W., (UMO-2011/03/B/NZ3/00693 and UMO-2013/10/E/NZ3/00670) for A.D. as well as The National Centre for Research and Development, grant STRATEGMED 3/305813/2/NCBR/2017 for A.D., (UMO-2014/13/B/NZ4/00199 and UMO-2016/22/E/NZ4/00650) for P.D. and by the European Union's Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement no. 665735 (Bio4Med) and by funding from the Polish Ministry of Science and Higher Education as part of 2016–2020 funds for the implementation of international projects (agreement no. 3548/H2020/COFUND/2016/2) for A.D., P.D., J.D. This work was also supported by the Internal Projects of the Children's Memorial Health Institute No S125/2012 for A.K.W.
Funding Information:
Recently, it has been proposed a multistep nature of the PTP complex opening involving first, a disassembly of ATP synthase dimers and second, a correct rearrangement of the C-ring in the IMM (). This is coherent with previous findings in which a reduced dimerization status of ATP synthase was detected in aging cells, thus prompting them to cell death (Daum et al., 2013). Indeed, it is reported that aging is intimately related to a decline of mitochondrial functions (Sun et al., 2016) and young, middle-aged and senescent cells own important mitochondrial differences in terms of IMM integrity and organization, as well as the oxidative state of proteins, mtDNA, and phospholipids; for instances, it has to be remarked that ATP synthase in young cells is mainly detected in dimeric and oligomeric structures (Daum et al., 2013) to fully support the energetic requirement of the cell and the correct curvature of the IMM. Recent findings award the synthasome assembly to PTP modulators, such as CypD and generally, to conditions preventing mitochondrial permeability transition (MPT) (Beutner et al., 2017); on the other hand, in senescent mitochondria, a highly dynamic transition from dimers to monomers occur (Daum et al., 2013).
Funding Information:
P.P. is grateful to Camilla degli Scrovegni for continuous support. P.P. is supported by the Italian Ministry of Education, University and Research; the Italian Ministry of Health; Telethon (GGP15219/B); the Italian Association for Cancer Research (AIRC: IG-18624); and by local funds from the University of Ferrara. S.M. is supported by "Fondazione Umberto Veronesi" and the Italian Ministry of Health. A.R. was supported by local funds from the University of Ferrara (FIR 2017), the Italian Ministry of Health and Italian Cystic Fibrosis Foundation (FFC # 20/2015). G.S. was supported by the grants Telethon (GEP12066 and GGP16026), Ricerca Finalizzata, Italian Ministry of Health (RF-2013-02359065), Association for Cancer Research (AIRC, IG13447); Biochemical and Biophysical Research Council (grants BB/L020874/1; BB/P018726/1) and the Wellcome Trust (097815/Z/11/Z). P.J.O. is also thankful to the Foundation for Science and Technology (Portugal), through FEDER/COMPETE funding (Grants POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-016659, and PTDC/DTP-FTO/2433/2014). V.A.S. acknowledges support from the Foundation for Science and Technology (Portugal), IF/01182/2015. The authors are deeply indebted to past and present collaborators.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Aging has been linked to several degenerative processes that, through the accumulation of molecular and cellular damage, can progressively lead to cell dysfunction and organ failure. Human aging is linked with a higher risk for individuals to develop cancer, neurodegenerative, cardiovascular, and metabolic disorders. The understanding of the molecular basis of aging and associated diseases has been one major challenge of scientific research over the last decades. Mitochondria, the center of oxidative metabolism and principal site of reactive oxygen species (ROS) production, are crucial both in health and in pathogenesis of many diseases. Redox signaling is important for the modulation of cell functions and several studies indicate a dual role for ROS in cell physiology. In fact, high concentrations of ROS are pathogenic and can cause severe damage to cell and organelle membranes, DNA, and proteins. On the other hand, moderate amounts of ROS are essential for the maintenance of several biological processes, including gene expression. In this review, we provide an update regarding the key roles of ROS–mitochondria cross talk in different fundamental physiological or pathological situations accompanying aging and highlighting that mitochondrial ROS may be a decisive target in clinical practice.
AB - Aging has been linked to several degenerative processes that, through the accumulation of molecular and cellular damage, can progressively lead to cell dysfunction and organ failure. Human aging is linked with a higher risk for individuals to develop cancer, neurodegenerative, cardiovascular, and metabolic disorders. The understanding of the molecular basis of aging and associated diseases has been one major challenge of scientific research over the last decades. Mitochondria, the center of oxidative metabolism and principal site of reactive oxygen species (ROS) production, are crucial both in health and in pathogenesis of many diseases. Redox signaling is important for the modulation of cell functions and several studies indicate a dual role for ROS in cell physiology. In fact, high concentrations of ROS are pathogenic and can cause severe damage to cell and organelle membranes, DNA, and proteins. On the other hand, moderate amounts of ROS are essential for the maintenance of several biological processes, including gene expression. In this review, we provide an update regarding the key roles of ROS–mitochondria cross talk in different fundamental physiological or pathological situations accompanying aging and highlighting that mitochondrial ROS may be a decisive target in clinical practice.
KW - Age-related neurodegenerative disorders
KW - Aging
KW - Anti-ROS intervention
KW - Antioxidant defense
KW - Mitochondria
KW - Mitochondrial dysfunction–related pathologies
KW - ROS
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U2 - 10.1016/bs.ircmb.2018.05.006
DO - 10.1016/bs.ircmb.2018.05.006
M3 - Article
C2 - 30072092
AN - SCOPUS:85048861986
SN - 1937-6448
VL - 340
SP - 209
EP - 344
JO - International Review of Cell and Molecular Biology
JF - International Review of Cell and Molecular Biology
ER -
