Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

Gottardi, Enrico; Agrimi, Gennaro; Goldmann, Ulrich; Fiume, Giuseppe; Lindinger, Sabrina; Sedlyarov, Vitaly; Srndic, Ismet; Gürtl, Bettina; Agerer, Benedikt; Kartnig, Felix; Scarcia, Pasquale; Noia, Maria Antonietta Di; Liñeiro, Eva; Rebsamen, Manuele; Wiedmer, Tabea; Bergthaler, Andréas; Palmieri, Luigi; Superti‐Furga, Giulio

doi:10.1038/s41467-020-19871-x

Cited by 95 publications

(97 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As clear evidences for the existence of a mitochondrial NAD + transporter were missing, nuclear/cytoplasmic and mitochondrial NAD + pools were considered to not be exchangeable [ 70 ]. The recent identification of the NAD + transporter SLC25A51 that localizes to the mitochondrial inner membrane has, however, demonstrated that a direct NAD + exchange between mitochondria and the cytoplasm is possible and potentially physiologically relevant for cells [ 71 , 72 , 73 ].…”

Section: Nad + Synthesis and Its Involvement Inmentioning

confidence: 99%

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Hopp

Hottiger

2021

Cells

View full text Add to dashboard Cite

Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD+)-dependent post-translational modification that is found on proteins as well as on nucleic acids. While ARTD1/PARP1-mediated poly-ADP-ribosylation has extensively been studied in the past 60 years, comparably little is known about the physiological function of mono-ADP-ribosylation and the enzymes involved in its turnover. Promising technological advances have enabled the development of innovative tools to detect NAD+ and NAD+/NADH (H for hydrogen) ratios as well as ADP-ribosylation. These tools have significantly enhanced our current understanding of how intracellular NAD dynamics contribute to the regulation of ADP-ribosylation as well as to how mono-ADP-ribosylation integrates into various cellular processes. Here, we discuss the recent technological advances, as well as associated new biological findings and concepts.

show abstract

Section: Nad + Synthesis and Its Involvement Inmentioning

confidence: 99%

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Hopp

Hottiger

2021

Cells

View full text Add to dashboard Cite

show abstract

“…MAS is responsible for transferring electrons from cytosolic NADH to mitochondrial NADH, as reducing equivalents (e.g., NAD(P)H) cannot directly cross the inner mitochondrial membrane. However, recent studies identified that SLC25A51 and SLC25A52 facilitate mitochondrial NAD + transport [ 62 , 63 , 64 ]. Subsequent activity of the MAS and/or UCP2 is required to export aspartate into the cytosol where it can be used as a proteinogenic source and/or a precursor for arginine and asparagine synthesis [ 65 , 66 ].…”

Section: Compartmentalized Amino Acid Metabolismmentioning

confidence: 99%

“…Cytosolic and mitochondrial amino acid exchange facilitated by mitochondrial transporters is critical for redox shuttle activity (e.g., MAS, FOCM). With the recent identification of key mitochondrial transporters required for amino acid and NAD+ exchange, including SLC25A51 and SLC25A52, we now have the tools necessary to dissect how amino acid redox shuttle activity and/or direct NAD + import influence compartmentalized redox homeostasis [ 62 , 63 , 64 , 65 , 66 , 209 , 211 ]. Several amino acid transporters are not yet known, including those for asparagine, tryptophan, alanine, methionine, phenylalanine, tyrosine, cysteine, and proline [ 206 ].…”

Section: Mitochondrial Amino Acid Carriersmentioning

confidence: 99%

Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism

2021

View full text Add to dashboard Cite

Mitochondria are central organelles that coordinate a vast array of metabolic and biologic functions important for cellular health. Amino acids are intricately linked to the bioenergetic, biosynthetic, and homeostatic function of the mitochondrion and require specific transporters to facilitate their import, export, and exchange across the inner mitochondrial membrane. Here we review key cellular metabolic outputs of eukaryotic mitochondrial amino acid metabolism and discuss both known and unknown transporters involved. Furthermore, we discuss how utilization of compartmentalized amino acid metabolism functions in disease and physiological contexts. We examine how improved methods to study mitochondrial metabolism, define organelle metabolite composition, and visualize cellular gradients allow for a more comprehensive understanding of how transporters facilitate compartmentalized metabolism.

show abstract

“…This database is popular for describing detailed data on the functional family, endogenous substances, tissue differential distribution (Figure 2 and Table 3). Due to its specific scope of describing the SLC transporter family, it has been frequently used to facilitate SLC-related studies (Girardi et al, 2020 2, it provides the functional family, organism-specific abundance, tissue-differential distribution of transporters, together with the scRNA sequencing atlas (described in Table 3).…”

Section: Knowledge Bases Describing a Specific Transporter Familymentioning

confidence: 99%

Feature, Function, and Information of Drug Transporter–Related Databases

Yin¹,

Li²,

et al. 2021

Drug Metab Dispos

View full text Add to dashboard Cite

With the rapid progress in pharmaceutical experiments and clinical investigations, extensive knowledge of drug transporters (DTs) has accumulated, which is valuable data for the understanding of drug metabolism and disposition. However, such data is largely dispersed in the literature, which hampers its utility and significantly limits its possibility for comprehensive analysis. A variety of databases have, therefore, been constructed to provide DT-related data, and they were reviewed in this study. First, several knowledge bases providing data regarding clinically important drugs and their corresponding transporters were discussed, which constituted the most important resources of DT-centered data. Second, some databases describing the general transporters and their functional families were reviewed. Third, various databases offering transporter information as part of their entire data collection were described.Finally, customized database functions that are available to facilitate DT-related research were discussed. This review provided an overview of the whole collection of DT-related databases, which might facilitate research on precision medicine and rational drug use. Significant StatementA collection of well-established databases related to DTs were comprehensively reviewed, which were organized according to their importance in drug ADME research. These databases could collectively contribute to the research on rational drug use.

show abstract

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

Cited by 95 publications

References 60 publications

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism

Feature, Function, and Information of Drug Transporter–Related Databases

Contact Info

Product

Resources

About