Van Doan 2023 Abstract IOC162: Difference between revisions

Latest revision as of 17:40, 18 September 2023

Van Doan K, Luongo TS, Mukherjee S, Baur JA (2023) Mouse cardiac mitochondria are resilient to Nampt-dependent NAD⁺ los. Mitochondr Physiol Network 28.02

Link: IOC162

Van Doan Khanh, Luongo Timothy S, Mukherjee Sarmistha, Baur Joseph A (2023)

Event: IOC162

Mitochondria are important in cardiac metabolism, generating most of the ATP (>95%) and accounting for one third of cardiomyocyte cell volume. Nicotinamide adenine dinucleotide (NAD⁺), a critical cofactor/co-substrate in series of biochemical processes of cellular metabolism and homeostasis, plays an essential role in mitochondrial function. NAD⁺ content declines in numerous aging-related disorders including cardiovascular diseases. The NAD⁺ biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme maintaining cellular NAD⁺ level. We tested how NAD⁺ depletion affects mitochondrial function of cardiomyocytes.

In vitro, H9C2 rat cardiomyocytes were treated with FK866, a Nampt inhibitor, to deplete cellular NAD⁺. For in vivo study, mitochondria were isolated from the heart ventricles of cardiac specific Nampt knockout (KO) mice. Mitochondrial respiration was measured by Oroboros instrument.

Mitochondria isolated from both rat cardiomyocytes treated with FK866 and Nampt KO hearts retained normal or slightly elevated respiratory capacity, even though cellular and mitochondrial NAD⁺ levels significantly declined. Interestingly, NAD⁺ precursor supplementation with nicotinamide riboside (NR) in mice rescued these phenotypes of Nampt KO cardiomyocytes. Mouse cardiomyocytes are able to adapt to low cellular NAD⁺ concentration to maintain their mitochondrial function, possibly via a compensatory mechanism.

• Keywords: NAD+, Mitochondria, Cardiomyocyte • Bioblast editor: Plangger M • O2k-Network Lab: US PA Philadelphia Baur JA

Labels: MiParea: Respiration

HRR: Oxygraph-2k

Affiliations

Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

@@ Line 1: / Line 1: @@
 {{Abstract
-|title=Van Doan K, Luongo TS, Mukherjee S, Baur JA (2023) Mouse cardiac mitochondria are resilient to Nampt-dependent NAD+ los. IOC162.
+|title=Van Doan K, Luongo TS, Mukherjee S, Baur JA (2023) Mouse cardiac mitochondria are resilient to Nampt-dependent NAD<sup>+</sup> los. Mitochondr Physiol Network 28.02
 |info=[https://wiki.oroboros.at/index.php/MiPNet28.02_IOC162_Schroecken_AT IOC162]
-|authors=Van Doan K, Luongo TS, Mukherjee S, Baur JA
+|authors=Van Doan Khanh, Luongo Timothy S, Mukherjee Sarmistha, Baur Joseph A
 |year=2023
 |event=IOC162
-|abstract=Mitochondria are important in cardiac metabolism, generating most of the ATP (>95%) and accounting for one third of cardiomyocyte cell volume. Nicotinamide adenine dinucleotide (NAD+), a critical cofactor/co-substrate in series of biochemical processes of cellular metabolism and homeostasis, plays an essential role in mitochondrial function. NAD+ content declines in numerous aging-related disorders including cardiovascular diseases. The NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme maintaining cellular NAD+ level. We tested how NAD+ depletion affects mitochondrial function of cardiomyocytes.
+|abstract=Mitochondria are important in cardiac metabolism, generating most of the ATP (>95%) and accounting for one third of cardiomyocyte cell volume. Nicotinamide adenine dinucleotide (NAD<sup>+</sup>), a critical cofactor/co-substrate in series of biochemical processes of cellular metabolism and homeostasis, plays an essential role in mitochondrial function. NAD<sup>+</sup> content declines in numerous aging-related disorders including cardiovascular diseases. The NAD<sup>+</sup> biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme maintaining cellular NAD<sup>+</sup> level. We tested how NAD<sup>+</sup> depletion affects mitochondrial function of cardiomyocytes.
-In vitro, H9C2 rat cardiomyocytes were treated with FK866, a Nampt inhibitor, to deplete cellular NAD+. For in vivo study, mitochondria were isolated from the heart ventricles of cardiac specific Nampt knockout (KO) mice. Mitochondrial respiration was measured by Oroboros instrument.
+In vitro, H9C2 rat cardiomyocytes were treated with FK866, a Nampt inhibitor, to deplete cellular NAD<sup>+</sup>. For ''in vivo'' study, mitochondria were isolated from the heart ventricles of cardiac specific Nampt knockout (KO) mice. Mitochondrial respiration was measured by Oroboros instrument.
-Mitochondria isolated from both rat cardiomyocytes treated with FK866 and Nampt KO hearts retained normal or slightly elevated respiratory capacity, even though cellular and mitochondrial NAD+ levels significantly declined. Interestingly, NAD+ precursor supplementation with nicotinamide riboside (NR) in mice rescued these phenotypes of Nampt KO cardiomyocytes.
+Mitochondria isolated from both rat cardiomyocytes treated with FK866 and Nampt KO hearts retained normal or slightly elevated respiratory capacity, even though cellular and mitochondrial NAD<sup>+</sup> levels significantly declined. Interestingly, NAD<sup>+</sup> precursor supplementation with nicotinamide riboside (NR) in mice rescued these phenotypes of Nampt KO cardiomyocytes.
-Mouse cardiomyocytes are able to adapt to low cellular NAD+ concentration to maintain their mitochondrial function, possibly via a compensatory mechanism.
+Mouse cardiomyocytes are able to adapt to low cellular NAD<sup>+</sup> concentration to maintain their mitochondrial function, possibly via a compensatory mechanism.
+|keywords=NAD+, Mitochondria, Cardiomyocyte
 |editor=[[Plangger M]]
+|mipnetlab=US PA Philadelphia Baur JA
 }}
 {{Labeling
@@ Line 18: / Line 20: @@
 }}
 == Affiliations ==
+::::Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.