Talk:Nicotinamide adenine dinucleotide

NADH or NAD+ transport through the mtIM

• Todisco et al., 2006 - Identification of the Mitochondrial NAD⁺ Transporter in Saccharomyces cerevisiae. The Journal of Biological Chemistry 281(3), 1524–1531.[1]

"The mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides, and cofactors across the inner mitochondrial membrane. In Saccharomyces cerevisiae, NAD⁺ is synthesized outside the mitochondria and must be imported across the permeability barrier of the inner mitochondrial membrane. However, no protein responsible for this transport activity has ever been isolated or identified. In this report, the identification and functional characterization of the mitochondrial NAD⁺ carrier protein (Ndt1p) is described. The NDT1 gene was overexpressed in bacteria. The purified protein was reconstituted into liposomes, and its transport properties and kinetic parameters were characterized. It transported NAD⁺ and, to a lesser extent, (d)AMP and (d)GMP but virtually not alpha-NAD⁺, NADH, NADP⁺, or NADPH. Transport was saturable with an apparent Km of 0.38 mM for NAD⁺. The Ndt1p-GFP was found to be targeted to mitochondria. Consistently with Ndt1p localization and its function as a NAD⁺ transporter, cells lacking NDT1 had reduced levels of NAD⁺ and NADH in their mitochondria and reduced activity of mitochondrial NAD⁺- requiring enzymes. Similar results were also found in the mitochondria of cells lacking NDT2 that encodes a protein (Ndt2p) displaying 70% homology with Ndt1p. The ndt1 ndt2 double mutant exhibited lower mitochondrial NAD⁺ and NADH levels than the single deletants and a more pronounced delay in growth on nonfermentable carbon sources. The main role of Ndt1p and Ndt2p is to import NAD⁺ into mitochondria by unidirectional transport or by exchange with intramitochondrially generated (d)AMP and (d)GMP."

• SGD - Saccharomyces genome database

https://www.yeastgenome.org/locus/S000001268

Mitochondrial NAD+ transporter; involved in the transport of NAD+ into the mitochondria (see also YEA6); member of the mitochondrial carrier subfamily; disputed role as a pyruvate transporter; has putative mouse and human orthologs; YIA6 has a paralog, YEA6, that arose from the whole genome duplication.

• Hou et al., 2010. Metabolic Impact of Increased NADH Availability in Saccharomyces cerevisiae [2]

"In the mitochondria, NADH is formed in the tricarboxylic acid (TCA) cycle and the reaction of the pyruvate dehydrogenase complex. Cytosolic NADH is oxidized by the glycerol-3-phosphate shuttle or the external cytosolic NADH dehydrogenases, which are part of the electron transport chain (21). NADH can be transported across the outer mitochondrial membrane (18, 19) but not across the inner mitochondrial membrane (39). Therefore, a dedicated internal mitochondrial NADH dehydrogenase is required to oxidize mitochondrial NADH as part of the electron transport chain (22)."

• Davila et al., 2018. Nicotinamide adenine dinucleotide is transported into mammalian mitochondria [3]

NADH dehydrogenases or NADH:quinone oxidoreductases

Complex I

• Present in mammals and plants, present in yeast such as Neurospora crassa, but absent in yeast such as Saccharomyces cerevisiae.
• Is a proton pump (transports H⁺)

• Videira and Duarte, 2001. On complex I and other NADH:ubiquinone reductases of Neurospora crassa mitochondria [4]

• Ryčovská et al., 2000. The respiratory complex I in yeast: Isolation of a geneNUO51 coding for the nucleotide-binding subunit of NADH: Ubiquinone oxidoreductase from the obligately aerobic yeast Yarrowia lipolytica [5]

We have isolated a gene NUO51 coding for a homologue of the nucleotide-binding subunit of mitochondrial respiratory chain linked NADH:ubiquinone oxidoreductase from the obligately aerobic yeast Yarrowia lipolytica."

"Recently, it has been shown that Y. lipolytica Andh2 cells lacking functional alternative NADH:ubiquinone oxidoreductase exhibit about 30 % of wild-type activity that may be completely inhibited by piericidin A"

Alternative NADH dehydrogenases

• Havird et al., 2019. Do angiosperms with highly divergent mitochondrial genomes have altered mitochondrial function? [6].

"Plant internal and external NADH dehydrogenases, DHin and DHex, at the mitochondrial inner membrane (mtIM), facing the matrix and intermembrane space respectively"

• Matus-Ortega et al., 2015. New complexes containing the internal alternative NADH dehydrogenase (Ndi1) in mitochondria of Saccharomyces cerevisiae [7]

"Mitochondria of Saccharomyces cerevisiae lack the respiratory complex I, but contain three rotenone-insensitive NADH dehydrogenases distributed on both the external (Nde1 and Nde2) and internal (Ndi1) surfaces of the inner mitochondrial membrane. These enzymes catalyse the transfer of electrons from NADH to ubiquinone without the translocation of protons across the membrane."

• Schertl and Braun, 2014. Respiratory electron transfer pathways in plant mitochondria [8]

"In plants, the ETC is especially intricate. Besides the “classical” oxidoreductase complexes (complex I–IV) and the mobile electron transporters cytochrome c and ubiquinone, it comprises numerous “alternative oxidoreductases.” Furthermore, several dehydrogenases localized in the mitochondrial matrix and the mitochondrial intermembrane space directly or indirectly provide electrons for the ETC."

"The alternative NAD(P)H dehydrogenases serve as alternative electron entry points of the plant ETC and may substitute complex I. They differ with respect to co-factor requirement and localization at the outer or inner surface of the inner mitochondrial membrane (external alternative NDs, internal alternative NDs). Some of the genes encoding alternative NDs are activated by light (Rasmusson et al., 2008; Rasmusson and Moller, 2011). The latter enzymes are considered to be important during photorespiration and all alternative enzymes during various stress conditions. Since none of the alternative oxidoreductases couple electron transfer with proton translocation across the inner mitochondrial membrane, their enzymatic function is believed to be important in the context of an overflow protection mechanism for the ETC which is especially relevant during high-light conditions."