TY - JOUR
T1 - Mitochondrial dynamic alterations regulate melanoma cell progression
AU - Dal Yontem, Fulya
AU - Kim, Sun Hee
AU - Ding, Zhen
AU - Grimm, Elizabeth
AU - Ekmekcioglu, Suhendan
AU - Akcakaya, Handan
N1 - Funding Information:
This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) Department of Science Fellowships and Grants Program 2214/A International Research Program (1059B141300804), Istanbul University Department of Scientific Research Projects (project no: 51467) and partly supported by The UT MD Anderson Cancer Center SPORE in Melanoma (NCI, P50 CA093459) (SE and EAG) and the Dr Miriam and Sheldon G. Adelson Medical Research Foundation (EAG).
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/2
Y1 - 2019/2
N2 - Research on mitochondrial fusion and fission (mitochondrial dynamics) has gained much attention in recent years, as it is important for understanding many biological processes, including the maintenance of mitochondrial functions, apoptosis, and cancer. The rate of mitochondrial biosynthesis and degradation can affect various aspects of tumor progression. However, the role of mitochondrial dynamics in melanoma progression remains controversial and requires a mechanistic understanding to target the altered metabolism of cancer cells. Therefore, in our study, we disrupted mitochondrial fission with mdivi-1, the reported inhibitor of dynamin related protein 1 (Drp1), and knocked down Drp1 and Mfn2 to evaluate the effects of mitochondrial dynamic alterations on melanoma cell progression. Our confocal study results showed that mitochondrial fission was inhibited both in mdivi-1 and in Drp1 knockdown cells and, in parallel, mitochondrial fusion was induced. We also found that mitochondrial fission inhibition by mdivi-1 induced cell death in melanoma cells. However, silencing Drp1 and Mfn2 did not affect cell viability, but enhanced melanoma cell migration. We further show that dysregulated mitochondrial fusion by Mfn2 knockdowns suppressed the oxygen consumption rate of melanoma cells. Together, our findings suggest that mitochondrial dynamic alterations regulate melanoma cell migration and progression.
AB - Research on mitochondrial fusion and fission (mitochondrial dynamics) has gained much attention in recent years, as it is important for understanding many biological processes, including the maintenance of mitochondrial functions, apoptosis, and cancer. The rate of mitochondrial biosynthesis and degradation can affect various aspects of tumor progression. However, the role of mitochondrial dynamics in melanoma progression remains controversial and requires a mechanistic understanding to target the altered metabolism of cancer cells. Therefore, in our study, we disrupted mitochondrial fission with mdivi-1, the reported inhibitor of dynamin related protein 1 (Drp1), and knocked down Drp1 and Mfn2 to evaluate the effects of mitochondrial dynamic alterations on melanoma cell progression. Our confocal study results showed that mitochondrial fission was inhibited both in mdivi-1 and in Drp1 knockdown cells and, in parallel, mitochondrial fusion was induced. We also found that mitochondrial fission inhibition by mdivi-1 induced cell death in melanoma cells. However, silencing Drp1 and Mfn2 did not affect cell viability, but enhanced melanoma cell migration. We further show that dysregulated mitochondrial fusion by Mfn2 knockdowns suppressed the oxygen consumption rate of melanoma cells. Together, our findings suggest that mitochondrial dynamic alterations regulate melanoma cell migration and progression.
KW - fission
KW - fusion
KW - melanoma
KW - migration
KW - mitochondrial dynamics
UR - http://www.scopus.com/inward/record.url?scp=85052926510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052926510&partnerID=8YFLogxK
U2 - 10.1002/jcb.27518
DO - 10.1002/jcb.27518
M3 - Article
C2 - 30256441
AN - SCOPUS:85052926510
SN - 0730-2312
VL - 120
SP - 2098
EP - 2108
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - 2
ER -