PXD070896-1

PXD070896 is an original dataset announced via ProteomeXchange.

Title	Loss of Atoh8 impairs macroautophagy
Description	The basic helix-loop-helix (bHLH) transcription factor ‘Atoh8’ is involved in the regulaton of several developmental processes and pathologies. It regulates organogenesis, reprogramming, stem cell fate determination, and cancer development. However, the mech anisms underlying these observations remain unclear. Unlike many tissue-specific bHLH factors, Atoh8 is ubiquitously expressed during development as well as in adult tissue. In this study, we explored whether Atoh8 modulates basic cellular functions, which may reveal a common mechanism that could explain the diverse observations reported in the literature. In the present study, our findings indicate that the loss of Atoh8 impairs autophagy. We observed differential expression of LC3B-II, TFEB, and accumulation of p62 in the absence or downregulation of Atoh8 in multiple cell lines. Moreover, mass spectrometric analysis of protein lysates from the tibialis anterior (TA) muscle in both wildtype and Atoh8 knockout mice revealed a significant downregulation of proteins associated with the initiation of autophagy (DEPTOR, PRAS40), autophagosome maturation (PDCD6IP, CHMP5), and autolysosomal degradation (NPC2, CTSB, CTSL). Additionally, the analysis indicated altered metabolism in the absence of Atoh8. Moreover, we determined that persistently elevated levels of reactive oxygen species (ROS) may be the primary factor contributing to the impairment of autophagy in the absence or downregulation of Atoh8.Overall, this study underscores that Atoh8 is a crucial regulator of autophagy, and its reduction or absence disrupts the autophagic process.
HostingRepository	PRIDE
AnnounceDate	2026-01-05
AnnouncementXML	Submission_2026-01-04_16:35:49.463.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Britta Eggers
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-18 09:04:53	ID requested
⏵ 1	2026-01-04 16:35:50	announced

10.3390/cells14241993;

Divvela SSK, Offei EB, Kadr H, Hausherr M, Eggers B, Rozanova S, Eisenacher M, Nguyen HD, Tuoc T, Bader V, Yang X, Zaehres H, Chen A, Nguyen HP, Winklhofer KF, Marcus K, Brand-Saberi B, Loss of Atoh8 Impairs Macroautophagy. Cells, 14(24):(2025) [pubmed]

submitter keyword: Metabolism, TFEB, Atoh8, ROS, Macroautophagy, p62,Autophagy

Katrin Marcus
contact affiliation	Medizinisches Proteom-Center, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany; 44801 Bochum, Germany
contact email	katrin.marcus@rub.de
lab head
Britta Eggers
contact affiliation	Ruhr University Bochum
contact email	britta.eggers@rub.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070896
     1. Label: PRIDE project
     2. Name: Loss of Atoh8 impairs macroautophagy