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Université de Fribourg

Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import

Finger, Yannik ; Habich, Markus ; Gerlich, Sarah ; Urbanczyk, Sophia ; Logt, Erik ; Koch, Julian ; Schu, Laura ; Lapacz, Kim Jasmin ; Ali, Muna ; Petrungaro, Carmelina ; Salscheider, Silja Lucia ; Pichlo, Christian ; Baumann, Ulrich ; Mielenz, Dirk ; Dengjel, Jörn ; Brachvogel, Bent ; Hofmann, Kay ; Riemer, Jan

In: The EMBO Journal, 2020, vol. 39, no. 19, p. e103889

Plasticity of the proteome is critical to adapt to varying conditions. Control of mitochondrial protein import contributes to this plasticity. Here, we identified a pathway that regulates mitochondrial protein import by regulated N-terminal processing. We demonstrate that dipeptidyl peptidases 8/9 (DPP8/9) mediate the N-terminal processing of adenylate kinase 2 (AK2) en route to mitochondria....

Université de Fribourg

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Dawoody Nejad, Ladan ; Stumpe, Michael ; Rauch, Monika ; Hemphill, Andrew ; Schneiter, Roger ; Bütikofer, Peter ; Serricchio, Mauro

In: Scientific Reports, 2020, vol. 10, no. 1, p. 8268

Sphingosine-1-phosphate is a signaling molecule involved in the control of cell migration, differentiation, survival and other physiological processes. This sphingolipid metabolite can be degraded by the action of sphingosine-1-phosphate lyase (SPL) to form hexadecenal and ethanolamine phosphate. The importance of SPL-mediated ethanolamine phosphate formation has been characterized in only...

Università della Svizzera italiana

ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress

Loi, Marisa ; Raimondi, Andrea ; Morone, Diego ; Molinari, Maurizio

In: Nature communications, 2019, vol. 10, p. 5058

The endoplasmic reticulum (ER) produces about 40% of the nucleated cell’s proteome. ER size and content in molecular chaperones increase upon physiologic and pathologic stresses on activation of unfolded protein responses (UPR). On stress resolution, the mammalian ER is remodeled to pre-stress, physiologic size and function on activation of the LC3-binding activity of the translocon...

Université de Fribourg

Parvalbumin expression in oligodendrocyte-like CG4 cells causes a reduction in mitochondrial volume, attenuation in reactive oxygen species production and a decrease in cell processes’ length and branching

Lichvarova, Lucia ; Blum, Walter ; Schwaller, Beat ; Szabolcsi, Viktoria

In: Scientific Reports, 2019, vol. 9, no. 1, p. 10603

Forebrain glial cells - ependymal cells and astrocytes -acquire upon injury- a “reactive” phenotype associated with parvalbumin (PV) upregulation. Since free radicals, e.g. reactive oxygen species (ROS) play a role in the pathogenesis of multiple sclerosis, and that PV-upregulation in glial cells is inversely correlated with the level of oxidative stress, we hypothesized that...

Università della Svizzera italiana

Quality control mechanisms of protein biogenesis : proteostasis dies hard

Bergmann, Timothy Jan ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478

The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...

Università della Svizzera italiana

Proteostasis : bad news and good news from the endoplasmic reticulum

Noack, Julia ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: Swiss medical weekly, 2014, vol. 144, p. w14001

The endoplasmic reticulum (ER) is an intracellular compartment dedicated to the synthesis and maturation of secretory and membrane proteins, totalling about 30% of the total eukaryotic cells proteome. The capacity to produce correctly folded polypeptides and to transport them to their correct intra- or extracellular destinations relies on proteostasis networks that regulate and balance the...