Mitochondrial NADP(H) generation is essential for proline biosynthesis

Author:

Zhu Jiajun1ORCID,Schwörer Simon1ORCID,Berisa Mirela2ORCID,Kyung Yeon Ju1ORCID,Ryu Keun Woo1ORCID,Yi Junmei3ORCID,Jiang Xuejun3,Cross Justin R.2,Thompson Craig B.1ORCID

Affiliation:

1. Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

2. The Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

3. Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Abstract

Providing for protein synthesis Compartmentalization of metabolic processes into organelles can have important consequences. Zhu et al. examined the role of the coenzyme nicotinamide adenine dinucleotide phosphate (NADP + ) and its reduced form (NADPH) in cultured human cells. They found that cells lacking NAD kinase 2, an enzyme needed to make NADPH, had decreased abundance of mitochondrial NADPH and proliferated slowly in culture medium with limited nutrients because of a lack of proline. Proline is made in the mitochondria, and thus a key function of NADPH in the mitochondria appears to be the synthesis of proline to sustain cellular protein synthesis. Science , abd5491, this issue p. 968

Funder

National Institutes of Health

National Cancer Institute

National Institute of Allergy and Infectious Diseases

Hunter Douglas Fellowship in Breast Cancer Research

BRIA Postdoctoral Researcher Innovation Grant

Human Frontier Science Program

Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center

European Molecular Biology Organization

Leukemia and Lymphoma Society

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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