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GPS2 Regulates Mitochondria Biogenesis via Mitochondria Retrograde Signaling and Chromatin Remodeling of Nuclear-Encoded Mitochondrial Genes

73 Pages Posted: 6 Apr 2018 Publication Status: Published

See all articles by Maria Dafne Cardamone

Maria Dafne Cardamone

Boston University - Department of Biochemistry

Bogdan Tanasa

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine; University of California, San Francisco (UCSF), School of Medicine, Division of Hematology/Oncology, Department of Pediatrics

Carly Cedarquist

Harvard University - Joslin Diabetes Center

Jiawen Huang

Sanford Burnham Prebys Medical Discovery Institute

Kiana Mahdaviani

Boston University - Department of Medicine

Wenbo Li

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine; University of Texas at Houston - Department of Biochemistry and Molecular Biology

Michael G. Rosenfeld

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine

Marc Liesa

Boston University - Department of Medicine; University of California, Los Angeles (UCLA) - David Geffen School of Medicine

Valentina Perissi

Boston University - Department of Biochemistry

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Abstract

As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-tonucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. Together, these findings reveal an unexpected layer of regulation of mitochondrial gene transcription as they uncover a novel mitochondria-nuclear communication pathway.

Suggested Citation

Cardamone, Maria Dafne and Tanasa, Bogdan and Cedarquist, Carly and Huang, Jiawen and Mahdaviani, Kiana and Li, Wenbo and Rosenfeld, Michael G. and Liesa, Marc and Perissi, Valentina, GPS2 Regulates Mitochondria Biogenesis via Mitochondria Retrograde Signaling and Chromatin Remodeling of Nuclear-Encoded Mitochondrial Genes (2018). Available at SSRN: https://ssrn.com/abstract=3155593 or http://dx.doi.org/10.2139/ssrn.3155593
This version of the paper has not been formally peer reviewed.

Maria Dafne Cardamone

Boston University - Department of Biochemistry ( email )

Boston, MA 02118
United States

Bogdan Tanasa

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine

La Jolla, CA
United States

University of California, San Francisco (UCSF), School of Medicine, Division of Hematology/Oncology, Department of Pediatrics

San Francisco
United States

Carly Cedarquist

Harvard University - Joslin Diabetes Center ( email )

One Joslin Place
Boston, MA
United States

Jiawen Huang

Sanford Burnham Prebys Medical Discovery Institute

10901 North Torrey Pines Road
La Jolla, CA
United States

Kiana Mahdaviani

Boston University - Department of Medicine

Boston, MA
United States

Wenbo Li

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine ( email )

La Jolla, CA
United States

University of Texas at Houston - Department of Biochemistry and Molecular Biology ( email )

Houston, TX
United States

Michael G. Rosenfeld

University of California, San Diego (UCSD) - Department of Cellular and Molecular Medicine ( email )

La Jolla, CA
United States

Marc Liesa

Boston University - Department of Medicine

Boston, MA
United States

University of California, Los Angeles (UCLA) - David Geffen School of Medicine

1000 Veteran Avenue, Box 956939
Los Angeles, CA 90095-6939
United States

Valentina Perissi (Contact Author)

Boston University - Department of Biochemistry ( email )

Boston, MA 02118
United States

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