Research Topic

Mitochondrial Injury and Energy Depletion in Gastrointestinal Disorders

About this Research Topic

Mitochondrial ATP production is an essential requirement of a plethora of energy dependent physiological processes among all eukaryotic cells. On the other hand recent advances highlighted the role of mitochondria as a central orchestrator of intracellular signal transduction including Ca2+ and cAMP signaling. However mitochondrial injury and the consequent depletion of intracellular ATP is a hallmark of several pathological conditions ranging from neurological and cardiovascular diseases to gastrointestinal disorders.

For example, in the case of acute pancreatitis, which is the most common inflammatory disease of the gastrointestinal tract with unacceptable high mortality rate, mitochondrial injury was shown as a key factor in the development of cellular injury. Both bile acids and non-oxidative ethanol metabolites – the two most common etiological factors responsible for ~80% of all cases – induced severe functional and morphological alterations in the mitochondria of acinar and ductal cells, the two epithelial cell types of the exocrine pancreas. The lack of ATP consequentially impaired energy dependent functions, such as enzyme or ion secretion in the acinar and ductal cells, respectively. Whereas supplementation of the intracellular ATP level, or prevention of mitochondrial damage using novel inhibitors of the mitochondrial permeability transition pore maintained cell function and remarkably decreased the disease severity.

However, other main GI disorders such as IBD was also shown to be effected by mitochondrial dysfunction. Enterocytes isolated from patients with IBD or experimental models of colitis have been shown to exhibit swollen mitochondria with irregular cristae. Moreover, strong bioenergetic failure and reduced ATP levels were also observed. However, whether these changes in mitochondrial structure and function is a result of the disease or whether they may play a role in the pathogenesis of inflammation still needs to be clarified.

On the other way around, gastrointestinal manifestations of mitochondrial disorders (MIDs) can be also observed. For example, poor appetite, constipation/diarrhoea, dysphagia, vomiting, gastroparesis, hepatopathy or the above mentioned pancreatitis were clearly linked to MIDs.

In this Research Topic we aim to focus on the central role of mitochondrial injury and energy depletion in gastrointestinal disorders and provide a wide selection of articles (reviews, original research articles, translational or clinical observations, commentaries and hypotheses) from the leading experts in the field, discussing key aspects of this important intracellular event including the initiation, downstream effects and potential prevention of mitochondrial injury in diverse gastrointestinal disorders.


Keywords: Mitochondia, ATP, calcium, gastrointestinal tract, mitochondrial membrane potential


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Mitochondrial ATP production is an essential requirement of a plethora of energy dependent physiological processes among all eukaryotic cells. On the other hand recent advances highlighted the role of mitochondria as a central orchestrator of intracellular signal transduction including Ca2+ and cAMP signaling. However mitochondrial injury and the consequent depletion of intracellular ATP is a hallmark of several pathological conditions ranging from neurological and cardiovascular diseases to gastrointestinal disorders.

For example, in the case of acute pancreatitis, which is the most common inflammatory disease of the gastrointestinal tract with unacceptable high mortality rate, mitochondrial injury was shown as a key factor in the development of cellular injury. Both bile acids and non-oxidative ethanol metabolites – the two most common etiological factors responsible for ~80% of all cases – induced severe functional and morphological alterations in the mitochondria of acinar and ductal cells, the two epithelial cell types of the exocrine pancreas. The lack of ATP consequentially impaired energy dependent functions, such as enzyme or ion secretion in the acinar and ductal cells, respectively. Whereas supplementation of the intracellular ATP level, or prevention of mitochondrial damage using novel inhibitors of the mitochondrial permeability transition pore maintained cell function and remarkably decreased the disease severity.

However, other main GI disorders such as IBD was also shown to be effected by mitochondrial dysfunction. Enterocytes isolated from patients with IBD or experimental models of colitis have been shown to exhibit swollen mitochondria with irregular cristae. Moreover, strong bioenergetic failure and reduced ATP levels were also observed. However, whether these changes in mitochondrial structure and function is a result of the disease or whether they may play a role in the pathogenesis of inflammation still needs to be clarified.

On the other way around, gastrointestinal manifestations of mitochondrial disorders (MIDs) can be also observed. For example, poor appetite, constipation/diarrhoea, dysphagia, vomiting, gastroparesis, hepatopathy or the above mentioned pancreatitis were clearly linked to MIDs.

In this Research Topic we aim to focus on the central role of mitochondrial injury and energy depletion in gastrointestinal disorders and provide a wide selection of articles (reviews, original research articles, translational or clinical observations, commentaries and hypotheses) from the leading experts in the field, discussing key aspects of this important intracellular event including the initiation, downstream effects and potential prevention of mitochondrial injury in diverse gastrointestinal disorders.


Keywords: Mitochondia, ATP, calcium, gastrointestinal tract, mitochondrial membrane potential


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

About Frontiers Research Topics

With their unique mixes of varied contributions from Original Research to Review Articles, Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author.

Topic Editors

Loading..

Submission Deadlines

31 January 2018 Abstract
30 June 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..

Topic Editors

Loading..

Submission Deadlines

31 January 2018 Abstract
30 June 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..
Loading..

total views article views article downloads topic views

}
 
Top countries
Top referring sites
Loading..

Comments

Loading..

Add a comment

Add comment
Back to top