title: Fast perinuclear clustering of mitochondria in oxidatively stressed human choriocarcinoma cells.
abstract: Mitochondrial dysfunction plays a crucial role in cell types that exhibit necrosis-like death after activation of their death program. Tumour necrosis factor (TNF) induces abnormal, perinuclear clustering of mitochondria from an evenly spread distribution throughout the cytoplasm. The mitochondria withdraw from the cell periphery and aggregate in a unipolar perinuclear cluster. TNF-induced mitochondrial clustering is caused by impaired kinesin-mediated transportation of mitochondria. In this report, we describe a novel activity of menadione (MEN), namely the induction of an altered spatial distribution of mitochondria in the choriocarcinoma JAR cells. Strikingly, 2 hours of cell exposition to menadione did not disrupt the integrity of the plasma membrane, while the intracellular ATP level significantly decreased. Control (untreated) cells displayed a typically scattered distribution of filamentary mitochondria inside the cell. After 2 hours of MEN treatment the spatial distribution of the mitochondria was markedly altered to an asymmetric perinuclear clustered distribution. Menadione-stressed cells displayed a highly asymmetrical perinuclear clustered distribution of the mitochondria. The exposure of cells to MEN also results in a change in shape of the mitochondria into a population of enlarged granular structures. The results of our study demonstrate that in JAR cells menadione causes mitochondria to translocate from the cell periphery into the perinuclear region several hours before disruption of cell membrane integrity and cell death.
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Hallmann
authors.forename: Ryszard
authors.initials: R
authors.lastname: Milczarek
authors.forename: Marcin
authors.initials: M
authors.lastname: Lipiński
authors.forename: Ewa
authors.initials: E
authors.lastname: Kossowska
authors.forename: Jan Henryk
authors.initials: JH
authors.lastname: Spodnik
authors.forename: Michał
authors.initials: M
authors.lastname: Woźniak
authors.forename: Takashi
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Jerzy
authors.initials: J
authors.lastname: Klimek
mesh_terms: D045744:Cell Line, Tumor / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism*; D002822:Choriocarcinoma; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*