Mitochondrial structure, function and dynamics are temporally controlled by c-Myc

Graves, JA and Wang, Y and Sims-Lucas, S and Cherok, E and Rothermund, K and Branca, MF and Elster, J and Beer-Stolz, D and van Houten, B and Vockley, J and Prochownik, EV (2012) Mitochondrial structure, function and dynamics are temporally controlled by c-Myc. PLoS ONE, 7 (5).

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Abstract

Although the c-Myc (Myc) oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS), the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored. We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion. A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC) are not entirely normalized. Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter. The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell. © 2012 Graves et al.

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Creators	Email	Pitt Username	ORCID
Graves, JA
Wang, Y
Sims-Lucas, S
Cherok, E
Rothermund, K
Branca, MF
Elster, J
Beer-Stolz, D
van Houten, B	bev15@pitt.edu	BEV15
Vockley, J	jerryvockley@pitt.edu	GEV1	0000-0002-8180-6457
Prochownik, EV	evp4@pitt.edu	EVP4