47 295

Cited 0 times in

Mitochondrial dysfunction via disruption of complex II activity during iron chelation-induced senescence-like growth arrest of Chang cells.

Yoon, YS; Cho, H; Lee, JH; Yoon, G
Annals of the New York Academy of Sciences, 1011123-132, 2004
Journal Title
Annals of the New York Academy of Sciences
When cells are deprived of iron, their growth is invariably inhibited. However, the mechanism involved remains largely unclear. Recently, we have reported that subcytotoxic concentration of deferoxamine mesylate (DFO), an iron chelator, specifically inhibited transition of Chang cell, a normal hepatocyte cell line, from G1 to S phase, which was accompanied by irreversible appearance of senescent biomarkers. To investigate factors responsible for the irreversible arrest, we examined mitochondrial activities because they require several irons for their proper structure and function. After exposure to 1 M DFO, total cellular ATP level was irreversibly decreased with concurrent disruption of mitochondrial membrane potential (DeltaPsim), implying that it might be one of the crucial factors involved in the arrest. DFO did not directly inhibit the mitochondrial respiratory activities in vitro. Among the respiratory activities, complex II activity was specifically inhibited through a down-regulation of the expression of its iron-sulfur subunit. We also observed that mitochondrial morphology was drastically changed to highly elongated form. Our results suggest that mitochondrial function is sensitive to cellular iron level and iron deprivation might be involved in inducing the senescent arrest. In addition, complex II, which is a part of both oxidative phosphorylation and the Krebs cycle, could be one of the critical factors that regulate mitochondrial function by responding to iron levels.
MeSH terms
Biological Markers*Cell AgingCell Cycle/drug effectsCell LineDeferoxamine/pharmacologyDown-RegulationElectron Transport Complex II/*physiologyHepatocytes/cytology/drug effects/*metabolismHumansIron/*metabolismIron Chelating Agents/pharmacologyMitochondria/drug effects/*metabolism/ultrastructureProtein Subunits/genetics/metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
조, 혜성이, 재호윤, 계순
Full Text Link
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.