Lipids and proteins in distinct colors

Visualizing suborganellar lipid distribution using correlative light and electron microscopy

  • H. Mathilda Lennartz
  • Suman Khan
  • André Nadler
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    • Paraspeckle condensates are membraneless nuclear organelles linked to stress responses and disease states. We demonstrate that paraspeckle assembly is tightly controlled by antagonism between TDP-43 and other paraspeckle proteins, through non-random distribution of TDP-43 binding sites on the scaffolding RNA NEAT1. Structural changes in NEAT1 or altered protein stoichiometry affect condensate formation, with implications for neurodegeneration.

      Research Briefing
    • How cells actively control the size of biomolecular condensates to facilitate biological processes remains poorly understood. We show that in the pyrenoid — a biomolecular condensate that mediates approximately one-third of global CO2 fixation in algae — the kinase KEY1 disrupts phase-separation interactions to dynamically control the condensate size setpoint across the cell cycle.

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    • A study establishes a correlative light and electron microscopy workflow that reveals how individual lipid species distribute across nanoscale membrane domains, uncovering sphingomyelin sorting within the early endosome.

      • Aubrey Weigel
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    • Tumour location dictates ferroptosis resistance. A study indicates that peritumoural adipose tissue aids tumours in evading ferroptosis by supplying tryptophan metabolites, including kynurenine and 3-hydroxykynurenine, which block NCOA4-mediated ferritinophagy to lower levels of labile iron and suppress lipid peroxidation.

      • Eikan Mishima
      • Marcus Conrad
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    • The lipid metabolism enzyme Ayr1 binds in a substrate-mimicry mechanism to the mitochondrial import (MIM) complex. Unlike typical MIM substrates that are inserted by the MIM complex into the mitochondrial outer membrane, Ayr1 remains bound to MIM to promote lipid droplet–mitochondria contacts and modulate lipid droplet homeostasis.

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  • Aditi U. Gurkar is an associate professor at the Aging Institute of the University of Pittsburgh, studying the mechanisms of ageing. We reached out to Aditi to discuss her career, perspective on the cellular ageing field, outreach efforts, and how to practice what we teach when it comes to longevity-promoting practices.

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  • Mitochondrial DNA (mtDNA) is not static but undergoes a regulated ‘life cycle’ that encompasses replication, maintenance, spatial distribution and turnover. Here, we update emerging mtDNA degradative pathways, discuss the interplay between mtDNA quality control and heteroplasmy, and outline crucial questions that place the mtDNA life cycle at the forefront of mitochondrial biology.

    • Luis Carlos Tábara
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A 3D-rendered image of a nucleus, showing distinct compartments of DNA in various colours within it.

4D nucleome

The 4D Nucleome (4DN) program, funded by the National Institutes of Health Common Fund, was established in 2015 to map the three-dimensional organization of the nucleus in space and time (the 4th dimension).
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