title: Multiscale modeling of tumorigenesis induced by mitochondrial incapacitation in cell death.
abstract: There is a renewed interest in tumorigenesis provoked by glycolysis and prosurvival autophagy following the mitochondrial permeability transition during cell death. To investigate such mitochondrial dysfunction, we have developed a multiscale model by integrating the dynamic behaviors of essential oncogenic proteins, cells, and their microenvironment. We found that 1) the concentration of cellular ATP (adenosine triphosphate) available during the autophagy-related processes is a critical factor in determining tumorigenesis; 2) mitochondrial aging rate has a significant influence on this tumorigenic effect, 3) specific hypoxic and oxidative stresses work cooperatively for tumorigenesis during cell death. We conclude that the cellular mitochondrial status is critical in triggering tumorigenesis during the cell death process, particularly under harsh microenvironments.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Safee U
authors.initials: SU
authors.lastname: Chaudhary
authors.forename: Sung-Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Won
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D059016:Tumor Microenvironment