About this Research Topic
Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. Mitochondrial fusion is a two-step process, where the outer and inner mitochondria fuse by separable events. This process can be explained by the finding that the most relevant proteins described to date that are involved in mammalian mitochondrial fusion show distinct mitochondrial sub-localization: mitofusin 1 and 2 (Mfn1 and Mfn2, respectively, located on the outer mitochondrial membrane, OMM, and can explain outer membrane fusion) and OPA1 (located in the inner membrane and intermembrane space, which can explain inner membrane fusion). Tethering of two mitochondria both precedes and enables OMM fusion. Mfn2 (but not Mfn1) can, however, also localize to endoplasmic reticulum, ER (and sarcoplasmic reticulum, SR, in cardiomyocytes), thereby tethering ER/SR to mitochondria and facilitating inter-organelle calcium signaling.
On the other hand, mitochondrial fission is driven by the cytosolic GTPase Dynamin-related protein 1 (DNM1L/Drp1), which is recruited to the OMM in a finely regulated process, also involving other proteins such as Fis1 and the mitochondrial fission factor (Mff).
A large bulk of evidence shows that Mfn2 is involved in mitochondrial metabolism, mitochondrial membrane potential maintenance and cellular oxygen consumption as well as substrate oxidation. Mfn2 loss-of-function reduces the activity of Krebs cycle and of the electron transport chain in such a way that the energy metabolism of the cell is compensated by a higher rate of glucose uptake and glycolysis and a lower rate of glycogen synthesis. Several lines of evidence support the view that Mfn2 exerts a regulatory role on the cell cycle. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (Mfn2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer's disease/autosomal dominant optic atrophy or ADOA). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired Mfn2 expression. Mfn2 is downregulated in skeletal muscle in human obesity and in obese Zucker rats, and this is accompanied by a reduction in mitochondrial size and in the extent of the mitochondrial network.
Drp1 mutation causes a lethal disease with severe clinical traits that may reflect defects in mitochondrial or in peroxisomal function, probably involved in the pathogenesis of the disease.
For these reasons, the study of mitochondrial dynamics offers an exciting and challenging field of study.
If mitochondrial dynamics proteins are involved in complex diseases, as endocrine pathologies, the possibility of using them as drug targets -especially for those proteins that are in the OMM oriented towards the cytosol- becomes a huge incentive to continue and deepen the studies and discoveries in mitochondrial dynamics. Therefore, this Research Topic Aims to highlight current advances in mitochondrial dynamics research in the form of Original Research, Review, Mini-Review and Perspective articles.
The aims of the proposed research topic are (but not limited to):
Mitochondrial Dynamics of:
1-Endocrine Disorders (e.g. diabetes, obesity)
2-Endocrine Systems and Hormones
3-Cancer
On the other hand, mitochondrial fission is driven by the cytosolic GTPase Dynamin-related protein 1 (DNM1L/Drp1), which is recruited to the OMM in a finely regulated process, also involving other proteins such as Fis1 and the mitochondrial fission factor (Mff).
A large bulk of evidence shows that Mfn2 is involved in mitochondrial metabolism, mitochondrial membrane potential maintenance and cellular oxygen consumption as well as substrate oxidation. Mfn2 loss-of-function reduces the activity of Krebs cycle and of the electron transport chain in such a way that the energy metabolism of the cell is compensated by a higher rate of glucose uptake and glycolysis and a lower rate of glycogen synthesis. Several lines of evidence support the view that Mfn2 exerts a regulatory role on the cell cycle. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (Mfn2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer's disease/autosomal dominant optic atrophy or ADOA). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired Mfn2 expression. Mfn2 is downregulated in skeletal muscle in human obesity and in obese Zucker rats, and this is accompanied by a reduction in mitochondrial size and in the extent of the mitochondrial network.
Drp1 mutation causes a lethal disease with severe clinical traits that may reflect defects in mitochondrial or in peroxisomal function, probably involved in the pathogenesis of the disease.
For these reasons, the study of mitochondrial dynamics offers an exciting and challenging field of study.
If mitochondrial dynamics proteins are involved in complex diseases, as endocrine pathologies, the possibility of using them as drug targets -especially for those proteins that are in the OMM oriented towards the cytosol- becomes a huge incentive to continue and deepen the studies and discoveries in mitochondrial dynamics. Therefore, this Research Topic Aims to highlight current advances in mitochondrial dynamics research in the form of Original Research, Review, Mini-Review and Perspective articles.
The aims of the proposed research topic are (but not limited to):
Mitochondrial Dynamics of:
1-Endocrine Disorders (e.g. diabetes, obesity)
2-Endocrine Systems and Hormones
3-Cancer
Keywords: mitochondrial fusion, mitochondrial fission, endocrine diseases, mitofusin 2, Drp1
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