Suppression of Cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.
To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10) interacts with heat shock protein 60 (HSP60) and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS) generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
So Jung
SJ
Park
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Doo Sin
DS
Jo
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Ji Hyun
JH
Shin
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Eun Sung
ES
Kim
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Yoon Kyung
YK
Jo
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Eun Sun
ES
Choi
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea; Department of Genetic Engineering, Kyung Hee University, Yongin, South Korea.
Hae Mi
HM
Seo
School of Medicine, Kyung Hee University, Seoul, South Korea.
Sung Hyun
SH
Kim
Asan Institute for Life Science, Institute for Innovative Cancer Research, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jung Jin
JJ
Hwang
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Dong-Gyu
DG
Jo
Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jae-Young
JY
Koh
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Dong-Hyung
DH
Cho
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018835:Chaperonin 10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D009574:Nitro Compounds / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D018835:Chaperonin 10; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009574:Nitro Compounds; D011422:Propionates; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; C015392:3-nitropropionic acid