Volume 23 Issue 12, December 2021

Mitochondrial-derived vesicles (MDVs) transfer mitochondrial content to lysosomes and peroxisomes. A study now reveals that MDVs deliver β-barrel proteins and fully assembled mitochondrial complexes for lysosomal degradation, establishing an important role for MDVs in mitochondrial protein quality control.

Extracellular vesicles and particles have important roles in physiology and disease. Advances in isolation and characterization technologies have enabled the identification of new particles. Supermeres are the newest addition to the rapidly expanding repertoire of the cell secretome, and provide exciting opportunities for clinical translation.

Rhythmic removal of circadian clock proteins is important for the strength and periodicity of the circadian rhythm. A study now reveals that chaperone-mediated autophagy regulates the degradation of circadian proteins, and is also transcriptionally regulated by the circadian machinery. This feedback loop helps to maintain circadian oscillations.

Formerly regarded as ‘junk’ DNA, transposable elements are now thought to be players in genome evolution. A new study reveals remarkable conservation of a retrotransposon insertion acting as an alternative promoter to drive the expression of a cell cycle regulator isoform in early embryos, potentially controlling the timing of pre-implantation development.

Gerber, Russ et al. show that the H3.3 chaperone Daxx, which represses endogenous retroviral and retrotransposable elements, acts as an epigenetic barrier to control haematopoietic progenitor plasticity and protect against PU.1-mediated inflammation.

Zhang et al. identify and characterize supermeres as extracellular nanoparticles that exhibit unique biological and functional properties with potential prognostic and therapeutic value across distinct diseases.

Juste, Kaushik and co-workers show that the circadian regulation of chaperone-mediated autophagy orchestrates the degradation of clock components and contributes to the circadian remodelling of the proteome.

By characterizing the composition of mitochondrial-derived vesicles (MDVs), König et al. define a MIRO1/2- and DRP1-dependent MDV biogenesis pathway and propose that MDVs maintain the mitochondrial proteome by shuttling assembled protein complexes to lysosomes.

Adamowicz et al. report that toxic PARP1 activity, induced by ataxia-associated mutations in XRCC1, impairs the recovery of global transcription during DNA base excision repair by promoting aberrant recruitment and activity of the histone ubiquitin protease USP3.

Fatehullah et al. develop transgenic and orthotopic mouse models to recapitulate advanced human gastric cancer and uncover a mechanistic role for Lgr5⁺ stem-like cells in promoting disease initiation and progression.

Wang et al. analysed post-mortem samples of the lungs of patients with COVID-19 by bulk and single-nucleus RNA sequencing along with proteomics and discovered lung senescence as a feature of COVID-19 pathology.

Jo et al. develop a broadly applicable deep-learning approach to predict fluorescence (FL) based on label-free refractive index (RI) measurements, ‘RI2FL’ (RI to FL). The trained model can be used across cell types without retraining.