Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity

Neeharika Nemani; Zhiwei Dong; Cassidy C. Daw; Travis R. Madaris; Karthik Ramachandran; Benjamin T. Enslow; Cherubina S. Rubannelsonkumar; Santhanam Shanmughapriya; Varshini Mallireddigari; Soumya Maity; Pragya SinghMalla; Kalimuthusamy Natarajanseenivasan; Robert Hooper; Christopher E. Shannon; Warren G. Tourtellotte; Brij B. Singh; W. Brian Reeves; Kumar Sharma; Luke Norton; Subramanya Srikantan; Jonathan Soboloff; Muniswamy Madesh

doi:10.1126/scisignal.aaz6206

Research ArticleMetabolism

Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity

View ORCID ProfileNeeharika Nemani¹,²,
Zhiwei Dong¹,²,
View ORCID ProfileCassidy C. Daw³,
View ORCID ProfileTravis R. Madaris³,
View ORCID ProfileKarthik Ramachandran³,
View ORCID ProfileBenjamin T. Enslow³,
View ORCID ProfileCherubina S. Rubannelsonkumar³,
View ORCID ProfileSanthanam Shanmughapriya¹,²,⁴,
View ORCID ProfileVarshini Mallireddigari¹,²,
Soumya Maity³,
Pragya SinghMalla³,
Kalimuthusamy Natarajanseenivasan¹,²,⁵,
Robert Hooper⁶,
View ORCID ProfileChristopher E. Shannon⁷,
Warren G. Tourtellotte⁸,
View ORCID ProfileBrij B. Singh⁹,
View ORCID ProfileW. Brian Reeves³,
View ORCID ProfileKumar Sharma³,
View ORCID ProfileLuke Norton⁷,
View ORCID ProfileSubramanya Srikantan³,
View ORCID ProfileJonathan Soboloff¹,⁶, and
View ORCID ProfileMuniswamy Madesh ¹,²,³,*

¹Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
²Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.
³Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
⁴Heart and Vascular Institute, Department of Medicine and Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17601, USA.
⁵Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
⁶Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.
⁷Department of Medicine/Diabetes Division, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
⁸Pathology & Laboratory Medicine, Neurology, Neurosurgery, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁹Department of Periodontics, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

↵*Corresponding author. Email: muniswamy{at}uthscsa.edu

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Science Signaling 21 Apr 2020:
Vol. 13, Issue 628, eaaz6206
DOI: 10.1126/scisignal.aaz6206

Neeharika Nemani

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

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ORCID record for Neeharika Nemani

Zhiwei Dong

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

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Cassidy C. Daw

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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ORCID record for Cassidy C. Daw

Travis R. Madaris

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Karthik Ramachandran

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Benjamin T. Enslow

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Cherubina S. Rubannelsonkumar

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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ORCID record for Cherubina S. Rubannelsonkumar

Santhanam Shanmughapriya

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

4Heart and Vascular Institute, Department of Medicine and Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17601, USA.

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Varshini Mallireddigari

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

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Soumya Maity

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Pragya SinghMalla

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Kalimuthusamy Natarajanseenivasan

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

5Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

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Robert Hooper

6Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.

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Christopher E. Shannon

7Department of Medicine/Diabetes Division, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Warren G. Tourtellotte

8Pathology & Laboratory Medicine, Neurology, Neurosurgery, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

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Brij B. Singh

9Department of Periodontics, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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W. Brian Reeves

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Kumar Sharma

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Luke Norton

7Department of Medicine/Diabetes Division, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Subramanya Srikantan

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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Jonathan Soboloff

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

6Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.

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Muniswamy Madesh

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

2Center for Translational Medicine, Lewis Katz School of Me.dicine at Temple University, Philadelphia, PA, 19140, USA.

3Department of Medicine/Nephrology Division, Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

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ORCID record for Muniswamy Madesh
For correspondence: muniswamy@uthscsa.edu

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