Metabolic Reprogramming During Neuronal Differentiation from Aerobic Glycolysis to Neuronal Oxidative Phosphorylation

Overview

Journal Elife

Specialty Biology

Date 2016 Jun 11

PMID 27282387

Citations 306

Authors

Xinde Zheng

Leah Boyer

Mingji Jin

Jerome Mertens

Yongsung Kim

Li Ma

Michael Hamm

Fred H Gage

Tony Hunter

Affiliations

Soon will be listed here.

Abstract

How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.

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