title: Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection.
abstract: Mitochondrial dysfunction is a hallmark of many diseases. The retrograde signaling initiated by dysfunctional mitochondria can bring about global changes in gene expression that alters cell morphology and function. Typically, this is attributed to disruption of important mitochondrial functions, such as ATP production, integration of metabolism, calcium homeostasis and regulation of apoptosis. Recent studies showed that in addition to these factors, mitochondrial dynamics might play an important role in stress signaling. Normal mitochondria are highly dynamic organelles whose size, shape and network are controlled by cell physiology. Defective mitochondrial dynamics play important roles in human diseases. Mitochondrial DNA defects and defective mitochondrial function have been reported in many cancers. Recent studies show that increased mitochondrial fission is a pro-tumorigenic phenotype. In this paper, we have explored the current understanding of the role of mitochondrial dynamics in pathologies. We present new data on mitochondrial dynamics and dysfunction to illustrate a causal link between mitochondrial DNA defects, excessive fission, mitochondrial retrograde signaling and cancer progression. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
authors.affiliation: The Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, #189E, Philadelphia, PA 19104, United States.
authors.forename: Satish
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: The Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, #189E, Philadelphia, PA 19104, United States.
authors.forename: Manti
authors.initials: M
authors.lastname: Guha
authors.affiliation: The Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, #189E, Philadelphia, PA 19104, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Kashina
authors.affiliation: The Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, #189E, Philadelphia, PA 19104, United States. Electronic address: narayan@vet.upenn.edu.
authors.forename: Narayan G
authors.initials: NG
authors.lastname: Avadhani
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000502:physiology; D020013:Calcium Signaling; D016764:Cell Polarity; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D052999:Quinazolinones / Q000494:pharmacology; D056811:Unfolded Protein Response
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D052999:Quinazolinones; D019703:Calcineurin
keywords: Mitochondrial dysfunction; cancer; mitochondrial dynamics; mitochondrial fission; retrograde signaling