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Assmann 2016 Cell Rep

From Bioblast
Publications in the MiPMap
Assmann N, Dettmer K, Simbuerger JM, Broeker C, Nuernberger N, Renner K, Courtneidge H, Klootwijk ED, Duerkop A, Hall A, Kleta R, Oefner PJ, Reichold M, Reinders J (2016) Renal fanconi syndrome is caused by a mistargeting-based mitochondriopathy. Cell Rep 15:1423-9.

ยป PMID: 27160910 Open Access

Assmann N, Dettmer K, Simbuerger JM, Broeker C, Nuernberger N, Renner K, Courtneidge H, Klootwijk ED, Duerkop A, Hall A, Kleta R, Oefner PJ, Reichold M, Reinders J (2016) Cell Rep

Abstract: We recently reported an autosomal dominant form of renal Fanconi syndrome caused by a missense mutation 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 ฮฒ-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.

Copyright ยฉ 2016 The Author(s). Published by Elsevier Inc. All rights reserved. โ€ข Keywords: Fanconi syndrome, Fatty acid oxidation, Mitochondriopathy, Supercomplexes, Pig kidney LLC-PK1 cells

โ€ข O2k-Network Lab: DE Regensburg Renner-Sattler K


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Other 

Organism: Pig  Tissue;cell: Kidney, Other cell lines  Preparation: Intact cells  Enzyme: Supercomplex 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, Other combinations, ROX  HRR: Oxygraph-2k 

2016-07