Assmann, Nadine and Dettmer, Katja and Simbuerger, Johann M. B. and Broeker, Carsten and Nuernberger, Nadine and Renner, Kathrin and Courtneidge, Holly and Klootwijk, Enriko D. and Duerkop, Axel and Hall, Andrew and Kleta, Robert and Oefner, Peter J. and Reichold, Markus and Reinders, Joerg (2016) Renal Fanconi Syndrome Is Caused by a Mistargeting-Based Mitochondriopathy. CELL REPORTS, 15 (7). pp. 1423-1429. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
We recently reported an autosomal dominant form of renal Fanconi syndrome caused by a missensemutation in the third codon of the peroxisomal protein EHHADH. The mutation mistargets EHHADH to mitochondria, thereby impairing mitochondrial energy production and, consequently, reabsorption of electrolytes and low-molecular-weight nutrients in the proximal tubule. Here, we further elucidate the molecular mechanism underlying this pathology. We find that mutated EHHADH is incorporated into mitochondrial trifunctional protein (MTP), thereby disturbing beta-oxidation of long-chain fatty acids. The resulting MTP deficiency leads to a characteristic accumulation of hydroxyacyl- and acylcarnitines. Mutated EHHADH also limits respiratory complex I and corresponding supercomplex formation, leading to decreases in oxidative phosphorylation capacity, mitochondrial membrane potential maintenance, and ATP generation. Activity of the Na+/K+-ATPase is thereby diminished, ultimately decreasing the transport activity of the proximal tubule cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FATTY-ACID OXIDATION; BETA-OXIDATION; 3-HYDROXYACYL-COA DEHYDROGENASE; TRIFUNCTIONAL PROTEIN; PHOSPHORYLATION; TUBULE; CELLS; COA; ATP; SPECIFICITY; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2019 09:55 |
| Last Modified: | 22 Mar 2019 09:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2931 |
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