Role of the mtDNA Mutations and Mitophagy in Inflammaging

Dabravolski, Siarhei A.; Nikiforov, Nikita G.; Zhuravlev, Alexander D.; Orekhov, Nikolay A.; Grechko, Andrey V.; Orekhov, Alexander N.

doi:10.3390/ijms23031323

Cited by 18 publications

(15 citation statements)

References 176 publications

(175 reference statements)

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“…Therefore, timely normalisation of the mitochondrial Zn 2+ level via downregulation or inactivation of the mitochondrial ZIP7 expression could be beneficial for patients with acute myocardial infarction and other cardiovascular diseases. Further, because impaired mitophagy is associated with many other diseases and disorders (such as Alzheimer's and Parkinson's diseases, premature ageing, atherosclerosis and others) [76,77], zinc-based modulation of the mitophagy rate with therapeutic or pharmacological approaches may have wide clinical applications.…”

Section: Zn 2+ Regulation Of Mitophagy In I/r Injurymentioning

confidence: 99%

Interplay between Zn2+ Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing

Dabravolski

Sadykhov

Kartuesov

et al. 2022

IJMS

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Zinc plays an important role in cardiomyocytes, where in exists in bound and histochemically reactive labile Zn2+ forms. Although Zn2+ concentration is under tight control through several Zn2+-transporters, its concentration and intracellular distribution may vary during normal cardiac function and pathological conditions, when the protein levels and efficacy of Zn2+ transporters can lead to zinc re-distribution among organelles in cardiomyocytes. Such dysregulation of cellular Zn2+ homeostasis leads to mitochondrial and ER stresses, and interrupts normal ER/mitochondria cross-talk and mitophagy, which subsequently, result in increased ROS production and dysregulated metabolic function. Besides cardiac structural and functional defects, insufficient Zn2+ supply was associated with heart development abnormalities, induction and progression of cardiovascular diseases, resulting in accelerated cardiac ageing. In the present review, we summarize the recently identified connections between cellular and mitochondrial Zn2+ homeostasis, ER stress and mitophagy in heart development, excitation–contraction coupling, heart failure and ischemia/reperfusion injury. Additionally, we discuss the role of Zn2+ in accelerated heart ageing and ageing-associated rise of mitochondrial ROS and cardiomyocyte dysfunction.

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Section: Zn 2+ Regulation Of Mitophagy In I/r Injurymentioning

confidence: 99%

Interplay between Zn2+ Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing

Dabravolski

Sadykhov

Kartuesov

et al. 2022

IJMS

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“…More AP sites result in green fluorescence with greater intensity and duration and the degree of mtdNA damage can be quantified based on the time of appearance and intensity of fluorescence at 480 nm. doxorubicin (dox), a common anticancer drug, not only causes damage to the nuclear dNA of cells but can also be rapidly inserted into the mtdNA of living cells, causing the aggregation of mtdNA nucleoids and changing the distribution of nuclear proteins (375)(376)(377)(378)(379)(380)(381)(382). Therefore, after dox induces mtdNA damage, morphological changes of mtdNA can be tracked in real time using the two-photon fluorescent probe CNQ, which emits red fluorescence and is localized to mtdNA.…”

Section: Measurement Of Rosmentioning

confidence: 99%

Common methods in mitochondrial research (Review)

Yin

Shen

2022

Int J Mol Med

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Mitochondrial abnormalities are primarily seen in morphology, structure and function. They can cause damage to organs, including the heart, brain and muscle, by various mechanisms, such as oxidative stress, abnormal energy metabolism, or genetic mutations. Identifying and detecting pathophysiological alterations in mitochondria is the principal means of studying mitochondrial abnormalities. The present study reviewed methods in mitochondrial research and focused on three aspects: Mitochondrial extraction and purification, morphology and structure and function. In addition to classical methods, such as electron microscopy and mitochondrial membrane potential monitoring, newly developed methods, such as mitochondrial ultrastructural determination, mtdNA mutation assays, metabolomics and analyses of regulatory mechanisms, have also been utilized in recent years. These approaches enable the accurate detection of mitochondrial abnormalities and provide guidance for the diagnosis and treatment of related diseases. Contents1. Introduction 2. Extraction and purification of mitochondria 3. determination of mitochondrial morphology and structure 4. determination of mitochondrial function 5.

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“…However, there is also evidence for a possible role of mtDNA displacement into the circulation in the pathogenesis of several conditions. In particular, a pattern of pro-inflammatory mediators pertaining to innate immune responses, including tumor necrosis factor alpha (TNF-α) and interferons (IFNs), have also been indicated to link cellular senescence with chronic low-grade inflammation [ 39 ]. In the next sections, the mechanisms of mtDNA release and the inflammatory signaling pathways elicited by circulating mtDNA molecules during aging and associated conditions are described.…”

Section: Mitochondrial Dna Mutations and Diseasesmentioning

confidence: 99%

“…Indeed, mtRNA−DNA hybrids that form during transcription, long stretches of ss-DNA, and R-loops containing RNA−DNA hybrids with a non-template ss-DNA are sensed and recognized by cGAS [ 73 ] ( Figure 2 ). The identification of high levels of pro-inflammatory mediators pertaining to innate immune responses in cellular senescence and chronic low-grade inflammation lends further support to a role of these mtDNA intermediates in triggering PRR-mediated responses [ 39 ]. However, their specific involvement in age-related conditions and senescence is currently unknown.…”

Section: Circulating Cell-free Mtdna: a Trigger Of Inflammationmentioning

confidence: 99%

Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions

Picca

Guerra

Calvani

et al. 2022

Cells

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Mitochondria are primarily involved in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. An immunostimulatory property of mitochondria has also been recognized which is deployed through the extracellular release of entire or portioned organelle and/or mitochondrial DNA (mtDNA) unloading. Dynamic homo- and heterotypic interactions involving mitochondria have been described. Each type of connection has functional implications that eventually optimize mitochondrial activity according to the bioenergetic demands of a specific cell/tissue. Inter-organelle communications may also serve as molecular platforms for the extracellular release of mitochondrial components and subsequent ignition of systemic inflammation. Age-related chronic inflammation (inflamm-aging) has been associated with mitochondrial dysfunction and increased extracellular release of mitochondrial components—in particular, cell-free mtDNA. The close relationship between mitochondrial dysfunction and cellular senescence further supports the central role of mitochondria in the aging process and its related conditions. Here, we provide an overview of (1) the mitochondrial genetic system and the potential routes for generating and releasing mtDNA intermediates; (2) the pro-inflammatory pathways elicited by circulating mtDNA; (3) the participation of inter-organelle contacts to mtDNA homeostasis; and (4) the link of these processes with senescence and age-associated conditions.

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Role of the mtDNA Mutations and Mitophagy in Inflammaging

Cited by 18 publications

References 176 publications

Interplay between Zn2+ Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing

Interplay between Zn2+ Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing

Common methods in mitochondrial research (Review)

Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions

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