Project 14:
The role of lysosomal protein degradation in mitochondrial membrane stress responses
Martin van der Laan
E-Mail: martin.van-der-laan@uks.eu
Phone: +49 6841-16-26590
Center for Molecular Signaling (PZMS), Medical Biochemistry & Molecular Biology
Saarland University
Dominic Winter
E-Mail: dominic.winter@uni-bonn.de
Phone: +49 228-287-7081
Institute for Biochemistry and Molecular Biology
University of Bonn
Abstract
Mitochondria are best known for critical roles in cellular metabolism and bioenergetics. Contemporary studies, however, also place mitochondria in the center of many intracellular signaling pathways and cell fate decisions. Yet little is known how they integrate into cellular quality control and stress response networks to sustain cellular homeostasis. In this project, we will examine the mutual links between mitochondrial membrane quality control systems and lysosomal functions, likely mediated by mitochondria-derived vesicles (MDVs).
Project-relevant publications
Akter F, Bonini S, Ponnaiyan S, Kögler-Mohrbacher B, Bleibaum F, Damme M, Renard BY, Winter D (2023) Multi-cell line analysis of lysosomal proteomes reveals unique features and novel lysosomal proteins. Mol Cell Proteomics. 22(3):100509.
Ebner M, Puchkov D, López-Ortega O, Muthukottiappan P, Su Y, Schmied C, Zillmann S, Nikonenko I, Koddebusch J, Dornan GL, Lucht MT, Koka V, Jang W, Koch PA, Wallroth A, Lehmann M, Brügger B, Pende M, Winter D, Haucke V (2023) Nutrient-regulated control of lysosome function by signaling lipid conversion. Cell. 186(24):5328-5346.e26.
Fielden LF, Busch JD, Merkt SG, Ganesan I, Steiert C, Hasselblatt HB, Busto JV, Wirth C, Zufall N, Jungbluth S, Noll K, Dung JM, Butenko L, von der Malsburg K, Koch HG, Hunte C, van der Laan M, Wiedemann N (2023) Central role of Tim17 in mitochondrial presequence protein translocation. Nature. 2023 Sep;621(7979):627-634.
von der Malsburg A, Sapp GM, Zuccaro KE, von Appen A, Moss FR 3rd, Kalia R, Bennett JA, Abriata LA, Dal Peraro M, van der Laan M, Frost A, Aydin H (2023) Structural mechanism of mitochondrial membrane remodelling by human OPA1. Nature. 620(7976):1101-1108.
Bock-Bierbaum T, Funck K, Wollweber F, Lisicki E, von der Malsburg K, von der Malsburg A, Laborenz J, Noel JK, Hessenberger M, Jungbluth S, Bernert C, Kunz S, Riedel D, Lilie H, Jakobs S, van der Laan M, Daumke O (2022) Structural insights into crista junction formation by the Mic60-Mic19 complex. Sci Adv. 8(35):eabo4946.
Rampelt H, Wollweber F, Licheva M, de Boer R, Perschil I, Steidle L, Becker T, Bohnert M, van der Klei I, Kraft C, van der Laan M, Pfanner N (2022) Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth. Cell Rep. 38(4):110290.
Richards CM, Jabs S, Qiao W, Varanese LD, Schweizer M, Mosen PR, Riley NM, Klüssendorf M, Zengel JR, Flynn RA, Rustagi A, Widen JC, Peters CE, Ooi YS, Xie X, Shi PY, Bartenschlager R, Puschnik AS, Bogyo M, Bertozzi CR, Blish CA, Winter D, Nagamine CM, Braulke T, Carette JE (2022) The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. Science. 378(6615):eabn5648.
Singh J, Elhabashy H, Muthukottiappan P, Stepath M, Eisenacher M, Kohlbacher O, Gieselmann V, Winter D (2022) Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo. Nat Commun. 13(1):6212.
Mosen P, Sanner A, Singh J, Winter D (2021) Targeted quantification of the lysosomal proteome in complex samples. Proteomes. 9(1):4.
Caumont-Sarcos A, Moulin C, Poinot L, Guiard B, van der Laan M, Ieva R (2020) Transmembrane coordination of preprotein recognition and motor coupling by the mitochondrial presequence receptor Tim50. Cell Rep. 30(9):3092-3104.e4.
Ponnaiyan S, Akter F, Singh J, Winter D (2020) Comprehensive draft of the mouse embryonic fibroblast lysosomal proteome by mass spectrometry based proteomics. Sci Data. 7(1):68.
Singh J, Kaade E, Muntel J, Bruderer R, Reiter L, Thelen M, Winter D (2020) Systematic comparison of strategies for the enrichment of lysosomes by data independent acquisition. J Proteome Res. 19(1):371-381.
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