TY - JOUR
T1 - Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and notch signaling
AU - Kasahara, Atsuko
AU - Cipolat, Sara
AU - Chen, Yun
AU - Dorn, Gerald W.
AU - Scorrano, Luca
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - Mitochondrial morphology is crucial for tissue homeostasis, but its role in cell differentiation is unclear. We found that mitochondrial fusion was required for proper cardiomyocyte development. Ablation of mitochondrial fusion proteins Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2 or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart development and impaired differentiation of ESCs into cardiomyocytes. Gene expression profiling revealed decreased levels of transcription factors transforming growth factor-β/bone morphogenetic protein, serum response factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca2+-dependent calcineurin activity and Notch1 signaling that impaired ESC differentiation. Orchestration of cardiomyocyte differentiation by mitochondrial morphology reveals how mitochondria, Ca 2+, and calcineurin interact to regulate Notch1 signaling.
AB - Mitochondrial morphology is crucial for tissue homeostasis, but its role in cell differentiation is unclear. We found that mitochondrial fusion was required for proper cardiomyocyte development. Ablation of mitochondrial fusion proteins Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2 or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart development and impaired differentiation of ESCs into cardiomyocytes. Gene expression profiling revealed decreased levels of transcription factors transforming growth factor-β/bone morphogenetic protein, serum response factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca2+-dependent calcineurin activity and Notch1 signaling that impaired ESC differentiation. Orchestration of cardiomyocyte differentiation by mitochondrial morphology reveals how mitochondria, Ca 2+, and calcineurin interact to regulate Notch1 signaling.
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U2 - 10.1126/science.1241359
DO - 10.1126/science.1241359
M3 - Article
C2 - 24091702
AN - SCOPUS:84887321199
SN - 0036-8075
VL - 342
SP - 734
EP - 737
JO - Science
JF - Science
IS - 6159
ER -