The Effects of Mitochondrial Dysfunction on the Cell Cycle

Mitochondria have many functions in addition to their canonical metabolic role of energy generation. Mitochondria exist in dynamic networks and their non-canonical roles include (but are not limited to) regulation of the cell cycle, intracellular calcium homeostasis, and apoptosis. In rapidly proliferating cells, mitochondria divide in coordination with nuclear division, a process called mitotic fission. Therefore, acquired dysfunctions of mitochondrial metabolism and dynamics (such as increased mitochondrial fission and reduced fusion) contribute to rapid cell cycle progression leading to hyperproliferative pathologies, such as cancers and pulmonary arterial hypertension, a benign cardiopulmonary disease.

Mitochondrial abnormalities in these diseases include increased pyruvate dehydrogenase kinase (PDK) and pyruvate kinase muscle isoform 2 (PKM2) expression, which in turn increase uncoupled glycolysis (the Warburg phenomenon). Warburg metabolism sustains energy homeostasis by the inhibition of oxidative metabolism that reduces mitochondrial apoptosis, allowing unchecked cell accumulation.

Furthermore, dysregulation of intramitochondrial Ca2+ due to epigenetic dysregulation of the mitochondrial calcium uniporter complex (MCUC) links the Warburg phenomenon to mitochondrial dynamics. Finally, targeting mitochondrial metabolism by promoting glucose oxidation, restoring fission/fusion balance, and regulating intramitochondrial calcium are promising therapeutic targets against hyperproliferative diseases.

The goal of this Research Topic is to help highlight research focusing on the effect of mitochondrial dynamics and metabolism on cell cycle regulation. In particular, studies identifying mitochondrial fission proteins (Drp1 and its binding partners) that may regulate cell cycle progression in health and in disease states are of particular interest. Also, we welcome submissions that help identify the relative importance of the mitochondrial fusion proteins (mitofusin isoforms) in regulating cell cycle progression in hyperproliferative diseases

Areas to be covered in this Research Topic may include, but are not limited to:

- Mediators of mitochondrial dynamics and diseases (Review Articles)
- Mitochondrial dynamics and cell division (Original Research Articles)
- Intramitochondrial calcium regulation in cell division (Original Research Articles)
- Mitochondrial regulation of the cytoskeleton in cell division (Review Articles)
- Effect of cell cycle inhibitors on mitochondrial dynamics (Review articles)
- Novel inhibitors and agonists of fission and fusion mediators to facilitate experimental therapeutics against hyperproliferative diseases (Original Research Articles)