TY - JOUR
T1 - Mitochondrial dynamics as regulators of cancer biology
AU - Trotta, Andrew Paul
AU - Chipuk, Jerry Edward
N1 - Funding Information:
This work was supported by: NIH Grants CA157740 (J. E. C.) and CA206005 (J. E. C.); the JJR Foundation, the William A. Spivak Fund, the Fridolin Charitable Trust, an American Cancer Society Research Scholar Award, a Leukemia and Lymphoma Society Career Development Award, and an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award. This work was also supported in part by two research Grants (5FY1174 and 1FY13416) from the March of Dimes Foundation, and the Developmental Research Pilot Project Program within the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai.
Publisher Copyright:
© 2017, Springer International Publishing.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive excessive proliferation, increase intracellular stress, and limit nutrient supply are all able to alter the bioenergetic and biosynthetic requirements of cancer cells. Consequently, mitochondrial function and shape rapidly adapt to these hostile conditions to support cancer cell proliferation and evade activation of cell death programs. In this review, we will discuss the molecular mechanisms governing mitochondrial dynamics and integrate recent insights into how changes in mitochondrial shape affect cellular migration, differentiation, apoptosis, and opportunities for the development of novel targeted cancer therapies.
AB - Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive excessive proliferation, increase intracellular stress, and limit nutrient supply are all able to alter the bioenergetic and biosynthetic requirements of cancer cells. Consequently, mitochondrial function and shape rapidly adapt to these hostile conditions to support cancer cell proliferation and evade activation of cell death programs. In this review, we will discuss the molecular mechanisms governing mitochondrial dynamics and integrate recent insights into how changes in mitochondrial shape affect cellular migration, differentiation, apoptosis, and opportunities for the development of novel targeted cancer therapies.
KW - Apoptosis
KW - Cancer
KW - Differentiation
KW - Migration
KW - Mitochondrial dynamics
KW - Oncogenic signaling
UR - http://www.scopus.com/inward/record.url?scp=85009291488&partnerID=8YFLogxK
U2 - 10.1007/s00018-016-2451-3
DO - 10.1007/s00018-016-2451-3
M3 - Review article
C2 - 28083595
AN - SCOPUS:85009291488
SN - 1420-682X
VL - 74
SP - 1999
EP - 2017
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 11
ER -