Publications by authors named "Michiel Krols"

Fluid preserved animal specimens in the collections of natural history museums constitute an invaluable archive of past and present animal diversity. Well-preserved specimens have a shelf-life spanning centuries and are widely used for e.g.

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Mitochondria interact with the ER at structurally and functionally specialized membrane contact sites known as mitochondria-ER contact sites (MERCs). Combining proximity labelling (BioID), co-immunoprecipitation, confocal microscopy and subcellular fractionation, we found that the ER resident SMP-domain protein ESYT1 was enriched at MERCs, where it forms a complex with the outer mitochondrial membrane protein SYNJ2BP. BioID analyses using ER-targeted, outer mitochondrial membrane-targeted, and MERC-targeted baits, confirmed the presence of this complex at MERCs and the specificity of the interaction.

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Mitochondrial-derived vesicles (MDVs) are implicated in diverse physiological processes-for example, mitochondrial quality control-and are linked to various neurodegenerative diseases. However, their specific cargo composition and complex molecular biogenesis are still unknown. Here we report the proteome and lipidome of steady-state TOMM20 MDVs.

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It has been over 20 years since the identification of the first GTPases that regulate mitochondrial fusion in drosophila, yeast, and mammalian cells. While the molecular identification of these players solidified the new field of mitochondrial dynamics, cell imaging had established the dynamic properties of mitochondria over a century before. The genetic dissection of mitochondrial fusion, fission, and positioning within cells cemented our understanding of the essential nature of this plasticity in health and disease.

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Axonopathies are neurodegenerative disorders caused by axonal degeneration, affecting predominantly the longest neurons. Several of these axonopathies are caused by genetic defects in proteins involved in the shaping and dynamics of the endoplasmic reticulum (ER); however, it is unclear how these defects impinge on neuronal survival. Given its central and widespread position within a cell, the ER is a pivotal player in inter-organelle communication.

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The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear.

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Article Synopsis
  • BIM is a pro-apoptotic protein that plays a crucial role in the intrinsic apoptosis pathway, and its levels are regulated during endoplasmic reticulum (ER) stress.
  • The study reveals that overexpressing heat shock protein B1 (HSPB1) leads to decreased BIM induction through enhanced degradation via the proteasome, dependent on MEK-ERK signaling.
  • Cells with mutations in HSPB1 related to Charcot-Marie-Tooth disease show increased vulnerability to ER stress and higher BIM levels, suggesting that normal HSPB1 functions to stabilize BIM and protect cells from apoptosis, a role disrupted by CMT mutations.
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ORMDL proteins are believed to be negative regulators of serine palmitoyltransferase (SPT), which catalyzes the first and rate limiting step in sphingolipid (SL) de novo synthesis. Several single-nucleotide polymorphisms (SNPs) that are close to the ORMDL3 locus have been reported to increase ORMDL3 expression and to be associated with an elevated risk for early childhood asthma; however, the direct effect of ORMDL3 expression on SPT activity and its link to asthma remains elusive. In this study, we investigated whether ORMDL3 expression is associated with changes in SPT activity and total SL levels.

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Endoplasmic reticulum (ER)-mitochondria membrane contacts are hotspots for calcium signaling. In this issue, Raturi et al. (2016.

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There is a growing appreciation that membrane-bound organelles in eukaryotic cells communicate directly with one another through direct membrane contact sites. Mitochondria-associated membranes are specialized subdomains of the endoplasmic reticulum that function as membrane contact sites between the endoplasmic reticulum and mitochondria. These sites have emerged as major players in lipid metabolism and calcium signaling.

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Article Synopsis
  • Schwann cells play a vital role in developing peripheral nerves by sorting and myelinating individual axons, but our understanding of their growth regulation during this process is still lacking.
  • Research shows that while the elimination of the mTOR protein in Schwann cells does not prevent the initiation of myelination, it significantly impairs the overall growth of these cells postnatally.
  • Consequently, the myelin sheath produced by mutant Schwann cells is thinner than normal, affecting axonal diameter and consequently reducing the conduction velocity in nerves.
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