Mitochondrial dynamics in cardiovascular disease: fission and fusion foretell form and function

Mitochondria maintain mitochondrial homeostasis through continuous fusion and fission, that is, mitochondrial dynamics, which is precisely mediated by mitochondrial fission and fusion proteins, including dynamin-related protein 1 (Drp1), mitofusin 1 and 2 (Mfn1/2), and optic atrophy 1 (OPA1). When the mitochondrial fission and fusion of cardiomyocytes are out of balance, they will cause their own morphology and function disorders, which damage the structure and function of the heart, are involved in the occurrence and progression of cardiovascular disease such as ischemia-reperfusion injury (IRI), septic cardiomyopathy, and diabetic cardiomyopathy. In this paper, we focus on the latest findings regarding the molecular features and regulatory mechanisms of mitochondrial dynamic disorder in cardiovascular pathologies. Finally, we will address how these findings can be applied to improve the treatment of cardiovascular disease.

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Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30

The Journal of Cell Biology ◽

10.1083/jcb.201907067 ◽

2020 ◽

Vol 219 (6) ◽

Cited By ~ 4

Author(s):

Yasmine J. Liu ◽

Rebecca L. McIntyre ◽

Georges E. Janssens ◽

Evan G. Williams ◽

Jiayi Lan ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Mitochondrial Network ◽

Mitochondrial Translation ◽

C Elegans ◽

Form And Function ◽

Unfolded Protein ◽

Lysosome Biogenesis ◽

And Function ◽

Protein Response ◽

Mitochondrial Unfolded Protein Response

Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by blocking fission or fusion synergizes with reduced mitochondrial translation to prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous disruption of fission and fusion abrogates the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic crosstalk between mitochondrial translation, mitochondrial dynamics, and lysosomal signaling in regulating longevity.

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Perturbed mitochondrial dynamics, an emerging aspect of epithelial-microbe interactions

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00031.2020 ◽

2020 ◽

Vol 318 (4) ◽

pp. G748-G762 ◽

Cited By ~ 1

Author(s):

Derek M. McKay ◽

Nicole L. Mancini ◽

Jane Shearer ◽

Timothy Shutt

Keyword(s):

Infectious Disease ◽

Cell Death ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Current Data ◽

Microbial Pathogens ◽

Mitochondrial Activity ◽

Mitochondrial Network ◽

Form And Function ◽

And Function

Mitochondria exist in a complex network that is constantly remodeling via the processes of fission and fusion in response to intracellular conditions and extracellular stimuli. Excessive fragmentation of the mitochondrial network because of an imbalance between fission and fusion reduces the cells’ capacity to generate ATP and can be a forerunner to cell death. Given the critical roles mitochondria play in cellular homeostasis and innate immunity, it is not surprising that many microbial pathogens can disrupt mitochondrial activity. Here we note the putative contribution of mitochondrial dysfunction to gut disease and review data showing that infection with microbial pathogens can alter the balance between mitochondrial fragmentation and fusion, preventing normal remodeling (i.e., dynamics) and can lead to cell death. Current data indicate that infection of epithelia or macrophages with microbial pathogens will ultimately result in excessive fragmentation of the mitochondrial network. Concerted research efforts are required to elucidate fully the processes that regulate mitochondrial dynamics, the mechanisms by which microbes affect epithelial mitochondrial fission and/or fusion, and the implications of this for susceptibility to infectious disease. We speculate that the commensal microbiome of the gut may be important for normal epithelial mitochondrial form and function. Drugs designed to counteract the effect of microbial pathogen interference with mitochondrial dynamics may be a new approach to infectious disease at mucosal surfaces.

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Mitochondrial Dynamics: The Intersection of Form and Function

Advances in Experimental Medicine and Biology - Mitochondrial Oxidative Phosphorylation ◽

10.1007/978-1-4614-3573-0_2 ◽

2012 ◽

pp. 13-40 ◽

Cited By ~ 34

Author(s):

Andrew Ferree ◽

Orian Shirihai

Keyword(s):

Mitochondrial Dynamics ◽

Form And Function ◽

And Function

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Regulation of Mitochondrial Dynamics by Aerobic Exercise in Cardiovascular Diseases

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.788505 ◽

2022 ◽

Vol 8 ◽

Author(s):

Changping Gu ◽

Jie Yan ◽

Liang Zhao ◽

Guanghan Wu ◽

Yue-lan Wang

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Aerobic Exercise ◽

Mitochondrial Function ◽

Cardiovascular Health ◽

Mitochondrial Dynamics ◽

Pharmaceutical Intervention ◽

Prevention And Treatment ◽

And Function ◽

Cvd Mortality

Mitochondrial dynamics, including continuous biogenesis, fusion, fission, and autophagy, are crucial to maintain mitochondrial integrity, distribution, size, and function, and play an important role in cardiovascular homeostasis. Cardiovascular health improves with aerobic exercise, a well-recognized non-pharmaceutical intervention for both healthy and ill individuals that reduces overall cardiovascular disease (CVD) mortality. Increasing evidence shows that aerobic exercise can effectively regulate the coordinated circulation of mitochondrial dynamics, thus inhibiting CVD development. This review aims to illustrate the benefits of aerobic exercise in prevention and treatment of cardiovascular disease by modulating mitochondrial function.

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Scanning tunneling microscopy (STM) of DNA and RNA

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152148 ◽

1989 ◽

Vol 47 ◽

pp. 34-35

Author(s):

Patricia G. Arscott ◽

Gil Lee ◽

Victor A. Bloomfield ◽

D. Fennell Evans

Keyword(s):

Molecular Structures ◽

Inorganic Materials ◽

Resolving Power ◽

Scanning Tunneling ◽

Tunneling Microscopy ◽

Form And Function ◽

Dna And Rna ◽

Calf Thymus ◽

And Function ◽

The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

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