Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

Giorgi, Carlotta; Marchi, Saverio; Simões, Inês C M; Ren, Zhijian; Morciano, Giampaolo; Perrone, Mariasole; Patalas-Krawczyk, Paulina; Borchard, Sabine; Jędrak, Paulina; Pierzynowska, Karolina; Szymański, Jan; Wang, David Q.; Portincasa, Piero; Węgrzyn, Grzegorz; Zischka, Hans; Dobrzyń, Paweł; Bonora, Massimo; Duszyński, Jerzy; Rimessi, Alessandro; Karkucińska-Więckowska, Agnieszka; Dobrzyń, Agnieszka; Szabadkai, György; Zavan, Barbara; Oliveira, Paulo J.; Sardão, Vilma A.; Pinton, Paolo; Wieckowski, Mariusz R.

doi:10.1016/bs.ircmb.2018.05.006

Cited by 281 publications

(191 citation statements)

References 806 publications

(847 reference statements)

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…The number of ER-mitochondrial contact sites was found to be lower in senescent cells [103]. This observation led to hypothesize that disruption of these contacts may have important implications for cell function and longevity [104].…”

Section: Nondegradative Pathwaysmentioning

confidence: 99%

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

View full text Add to dashboard Cite

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca 2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson's disease as a prototypical geroscience condition.Cells 2020, 9, 598 2 of 18 instability, telomere attrition, epigenetic alterations, deregulated nutrient sensing, and stem cell exhaustion [3]. According to the geroscience hypothesis, perturbations in these mechanisms increase the susceptibility to most chronic diseases, functional loss, and eventually, death [4]. Hence, these biologic pillars represent ideal targets for interventions to foster healthy aging [5,6].Mitochondrial dysfunction has attracted considerable interest as a target for geroprotective interventions. Indeed, mitochondria play sensor-transducer-effector roles in a multitude of biological processes, including integration of cell death signaling and preservation of cell stemness [7,8]. Albeit long considered to be standalone organelles, a great deal of evidence indicates that mitochondria interact physically and functionally with other cellular compartments via membrane contact sites and tethering molecules [9,10]. In particular, mitochondria establish connections with the endosomal compartment [11,12] and lysosomes [13,14]. These interactions support cytosolic shuttle systems of ions and metabolites across organelles [10,15], and participate to the regulation of cellular housekeeping processes [13,14].The mitochondrial-lysosomal axis is a major actor in mitochondrial quality control (MQC), a hierarchical network of pathways that ensure organellar homeostasis through the coordination of mitochondrial proteostasis, dynamics, biogene...

show abstract

Section: Nondegradative Pathwaysmentioning

confidence: 99%

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…A consequence of AS is ischemic heart disease (IHD), where the full or partial recovery of myocardial function is always difficult to achieve due to severe mitochondrial impairment [75,76]. Events consisting of I/R phases are accompanied by oxidative stress, pH changes, and cytosolic and mitochondrial Ca 2+ overload, which lead to the opening of the mitochondrial permeability transition pore complex (PTPC) and contribute to cardiomyocyte death [12,[77][78][79][80].…”

Section: Ischemic Heart Diseasementioning

confidence: 99%

“…Recent advances in the identification of the molecular partners regulating Ca 2+ dynamics in the mitochondrial compartment have helped elucidate the critical contributions of mitochondria to (patho) physiological conditions that rely on mitochondrial Ca 2+ oscillations [11]. Mitochondria are also the primary sources of intracellular reactive oxygen species (ROS) [12]. These dangerous species are produced in the electron transport chain (ETC) due to the partial reduction of oxygen to superoxide by complex I and complex III and are very harmful to cells.…”

mentioning

confidence: 99%

Mitophagy in Cardiovascular Diseases

Morciano

Patergnani

Bonora

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.

show abstract

“…In eukaryotes, mitochondria are the major source of reactive oxygen species (ROS) and they require specific onsite protection (22)(23)(24). Melatonin is a suitable selection for this purpose due to its antioxidative potency and its availability (25).…”

Section: Introductionmentioning

confidence: 99%

Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells

2019

View full text Add to dashboard Cite

It was a surprising discovery when mitochondria, as the power houses of cells, were also found to synthesize the potent mitochondrial targeted antioxidant, melatonin. The melatonin synthetic enzyme serotonin N-acetyltransferase (SNAT) was found in matrix and also in the intermembrane space of mitochondria. We hypothesize that the melatonin synthesis occurs in the matrix due to substrate (N-acetyl co-enzyme A) availability while the intermembrane space may serve as the recycling pool of SNAT to regulate the melatonin circadian rhythm. Another surprise was that the melatonin membrane receptors, including MT1 and MT2, were also present in mitochondria. The protective effects of melatonin against neuronal injury induced by brain ischemia/reperfusion were proven to be mainly mediated by mitochondrial melatonin receptors rather than the cell surface membrane receptors which is contrary to the classical principle. In addition, melatonin metabolic enzyme has also been identified in the mitochondria. This enzyme can convert melatonin to N-acetylserotonin to strengthen the antitumor effects of melatonin. Thus, mitochondria are the generator, battle ground and metabolic sites of melatonin. The biological significance of the strong association between mitochondria and melatonin should be intensively investigated.

show abstract

Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

Cited by 281 publications

References 806 publications

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Mitophagy in Cardiovascular Diseases

Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells

Contact Info

Product

Resources

About