Mechanism on Elongated Mitochondria Formation during Iorn Chelation-Induced Senescent Arrest

Enlarged or giant mitochondria have often been documented in aged tissues and several human disease harboring impaired function, although their role and the mechanism involved remain unclear. Recently, we observed progressive changes of mitochondrial morphology to highly elongated form during iron chelation-induced senescence-associated growth arrest of Chang cells. Interestingly, addition of H₂O₂ (200uM) was enough to induce mitochondrial elongation with cellular senescent phenotypes, whereas ethidium bromide (100ng/ml) which was employed to damage mtDNA only reformed cristae structure. TTFA, which is known to complexⅡ inhibitor was induced fragmentation of mitochondria. Elongated giant mitochondria also found in old human diploid fibroblast. Next, we examined expression levels of Drp1 and Mfn proteins, which are known as molecules directly regulating mitochondrial fission and fusion process, respectively. The total cellular expression levels of Drp1 was not significantly changed or decreased, showing diversity of its regulation depending on the stress, whereas expression level of Mfn2 increased in all senescent systems employed. Finally, the increased expression level of Mfn1 and Mfn2 proteins were also observed in the aging process of Sprague-Dawley rats. Taken together, we propose that formation of elongated mitochondria is one of common phenomena developed in the cellular progress to senescence or aging and it might be promoted through ROS production and through enhanced fusion process mediated by a shifted balance of Mfn/Drp1 expression ratio toward Mfn proteins. Additionally, we observed the interaction between Drp1 and GSK3β and also found phosphorylation of Drp1, providing the clue of Drp1 regulation by GSK3β.

Author dc:creator

• 윤, 동선

Contributors dc:contributor

• 윤, 계순
• 대학원 의학과
• 200324277

• 미토콘드리아
• 세포 노화
• mitofusin
• fusion
• Drp1
• Mitochondria
• cellular senescence

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000095
000000000095

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/2306