Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy

Wei, Xing; Chang, Andrew Chia Hao; Chang, Haishuang; Xu, Shan; Xue, Yilin; Zhang, Yuanxin; Lei, Ming; Chang, Alex Chia Yu; Zhang, Qingyong

doi:10.3389/fcvm.2022.800185

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…The Cx43 distribution was demonstrated to change in a diabetic cardiomyopathy murine model, with Cx43 amounts decreasing at the plasma membrane and increasing on the inner mitochondrial membrane. [111]. However, in diabetic retinopathy model, rat retinal endothelial cells grown in high glucose showed reduced mitochondrial Cx43 localization to the inner mitochondrial membrane [41].…”

Section: Pathophysiological Significance Of Mitochondrial Cx43mentioning

confidence: 98%

Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure

Cetin-Ferra

Francis

Cooper

et al. 2023

IJMS

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Mitochondria contain connexins, a family of proteins that is known to form gap junction channels. Connexins are synthesized in the endoplasmic reticulum and oligomerized in the Golgi to form hemichannels. Hemichannels from adjacent cells dock with one another to form gap junction channels that aggregate into plaques and allow cell–cell communication. Cell–cell communication was once thought to be the only function of connexins and their gap junction channels. In the mitochondria, however, connexins have been identified as monomers and assembled into hemichannels, thus questioning their role solely as cell–cell communication channels. Accordingly, mitochondrial connexins have been suggested to play critical roles in the regulation of mitochondrial functions, including potassium fluxes and respiration. However, while much is known about plasma membrane gap junction channel connexins, the presence and function of mitochondrial connexins remain poorly understood. In this review, the presence and role of mitochondrial connexins and mitochondrial/connexin-containing structure contact sites will be discussed. An understanding of the significance of mitochondrial connexins and their connexin contact sites is essential to our knowledge of connexins’ functions in normal and pathological conditions, and this information may aid in the development of therapeutic interventions in diseases linked to mitochondria.

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Section: Pathophysiological Significance Of Mitochondrial Cx43mentioning

confidence: 98%

Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure

Cetin-Ferra

Francis

Cooper

et al. 2023

IJMS

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“…Subsequently, other groups have confirmed the presence of Cx43 within mitochondria of various origins, including brown adipose tissue, astrocytes, and liver [133][134][135]. However, most research has been focused on heart tissue [136][137][138]. As of now, there are still no patch-clamp data available on Cx43-formed channels in mitoplasts [139].…”

Section: Mitochondrial Cx43mentioning

confidence: 99%

Gap Junctions or Hemichannel-Dependent and Independent Roles of Connexins in Fibrosis, Epithelial–Mesenchymal Transitions, and Wound Healing

Li,

Acosta,

Jiang

2023

Biomolecules

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Fibrosis initially appears as a normal response to damage, where activated fibroblasts produce large amounts of the extracellular matrix (ECM) during the wound healing process to assist in the repair of injured tissue. However, the excessive accumulation of the ECM, unresolved by remodeling mechanisms, leads to organ dysfunction. Connexins, a family of transmembrane channel proteins, are widely recognized for their major roles in fibrosis, the epithelial–mesenchymal transition (EMT), and wound healing. Efforts have been made in recent years to identify novel mediators and targets for this regulation. Connexins form gap junctions and hemichannels, mediating communications between neighboring cells and inside and outside of cells, respectively. Recent evidence suggests that connexins, beyond forming channels, possess channel-independent functions in fibrosis, the EMT, and wound healing. One crucial channel-independent function is their role as the primary functional component for cell adhesion. Other channel-independent functions of connexins involve their roles in mitochondria and exosomes. This review summarizes the latest advances in the channel-dependent and independent roles of connexins in fibrosis, the EMT, and wound healing, with a particular focus on eye diseases, emphasizing their potential as novel, promising therapeutic targets.

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“…Furthermore, Cx43 is detected within mitochondria isolated from stem cell antigen-1 + ( Lu et al, 2010 ) and H9c2 cells ( Tu et al, 2017 ; Pecoraro et al, 2021 ), from brown adipose tissue ( Kim et al, 2017 ), from astrocytes ( Kozoriz et al, 2010 ) and brain ( Azarashvili et al, 2011 ) as well as from liver ( Li et al, 2021 ). Most studies, however, focused on the mitochondrial localization of Cx43 in the heart ( Boengler et al, 2005 ; Gorbe et al, 2011 ; Srisakuldee et al, 2014 ; Shan et al, 2015 ; Gadicherla et al, 2017 ; Wang et al, 2019 ; He et al, 2021 ; Wei et al, 2022 ) including neonatal cardiomyocytes ( Tu et al, 2017 ) and embryonic stem cell-derived cardiomyocytes ( Wang et al, 2021 ). Mitochondria from mice with inducible Cx43 knockout ( Boengler et al, 2005 ; Gadicherla et al, 2017 ; Wang et al, 2019 ) or mice in which Cx43 was replaced by Cx32 ( Miro-Casas et al, 2009 ) served as respective negative controls.…”

Section: Presence Of Connexins Within Mitochondriamentioning

confidence: 99%

Connexin 43 in Mitochondria: What Do We Really Know About Its Function?

et al. 2022

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Connexins are known for their ability to mediate cell-cell communication via gap junctions and also form hemichannels that pass ions and molecules over the plasma membrane when open. Connexins have also been detected within mitochondria, with mitochondrial connexin 43 (Cx43) being the best studied to date. In this review, we discuss evidence for Cx43 presence in mitochondria of cell lines, primary cells and organs and summarize data on its localization, import and phosphorylation status. We further highlight the influence of Cx43 on mitochondrial function in terms of respiration, opening of the mitochondrial permeability transition pore and formation of reactive oxygen species, and also address the presence of a truncated form of Cx43 termed Gja1-20k. Finally, the role of mitochondrial Cx43 in pathological conditions, particularly in the heart, is discussed.

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Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy

Cited by 8 publications

References 51 publications

Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure

Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure

Gap Junctions or Hemichannel-Dependent and Independent Roles of Connexins in Fibrosis, Epithelial–Mesenchymal Transitions, and Wound Healing

Connexin 43 in Mitochondria: What Do We Really Know About Its Function?

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