PXD059459-1

PXD059459 is an original dataset announced via ProteomeXchange.

Title	Trypanosoma brucei Mic40 depletome
Description	Molecules that contribute to membrane curvature are essential for the formation of cristae, the bioenergetic subcompartments of mitochondria. Mic60 may be the oldest of these factors as its prokaryotic ortholog is also needed for bioenergetic-subcompartment formation in extant alphaproteobacteria, the closest organismal relatives to mitochondria. In prokaryotes and eukaryotes, Mic60 exhibits an invariable structure: the characteristic C-terminal mitofilin domain, a central coiled coil, and N-proximal transmembrane domain. Moreover, mitochondrial Mic60 is a central subunit of virtually all iterations of the crista-shaping MICOS multiprotein complex. Yet, no mic60 is detected in any genomes of Euglenozoa, an expansive phylum containing trypanosomes. Here, we show that Mic60 has been replaced in euglenazoans by two cryptic mitofilin-containing MICOS subunits, Mic34 and Mic40. Sharply contrasting Mic60 from two domains of life, these are not integral membrane proteins. Reverse genetics revealed they are intertwined with the oxidative folding protein import pathway required for mitochondrial–and crista–biogenesis, likely masking a potential membrane remodeling role. Nevertheless, Mic34 binds to phospholipid bilayers in vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like prokaryotic and eukaryotic Mic60. Astoundingly, Mic34 overexpression transiently elaborates the simplified tubular mitochondrion of a life cycle stage of Trypanosoma brucei with repressed oxidative phosphorylation. Using Mic34’s mitofilin structural homology to Mic60’s, we predicted mutations to a conserved mitofilin motif that ablated Mic34’s mitochondria-remodeling activity. Thus, we have expanded the mitofilin family of proteins to encompass diverged proteins that unconventionally implement mitofilin in nature.
HostingRepository	PRIDE
AnnounceDate	2025-12-01
AnnouncementXML	Submission_2025-11-30_16:41:30.439.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Corinna Benz
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: NEWT:5691;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-06 01:50:31	ID requested
⏵ 1	2025-11-30 16:41:31	announced

Sheikh S, Turpin Knotkov, á B, Benz C, Eli, á, š M, B, í, l, ý T, Bondar A, Tesa, ř, ov, á M, St, ř, í, brn, á E, Heller J, Meinecke M, Hashimi H, The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa. Mol Biol Evol, 42(11):(2025) [pubmed]

10.1093/molbev/msaf289;

submitter keyword: MICOS,trypanosoma, mitofilin

Julius Lukes
contact affiliation	Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice (Budweis) 370 05, Czech Republic
contact email	jula@paru.cas.cz
lab head
Corinna Benz
contact affiliation	Institute of Parasitology Biology Center, Czech Academy of Sciences Branišovská 31 370 05 České Budějovice
contact email	corinna.benz@paru.cas.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD059459

PRIDE project URI

• PRIDE
  1. PXD059459
     1. Label: PRIDE project
     2. Name: Trypanosoma brucei Mic40 depletome