Dataset Information

Trypanosoma brucei Mic40 depletome

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Trypanosoma Brucei

SUBMITTER: Corinna Benz

LAB HEAD: Julius Lukes

PROVIDER: PXD059459 | Pride | 2025-12-01

REPOSITORIES: Pride

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			Action	DRS
	PLK193_OE480_231030_BC_CB_dpi3_1_1-7uL_DIA-FAIMS_120M_90G.raw	Raw
	PLK193_OE480_231030_BC_CB_dpi3_2_1-7uL_DIA-FAIMS_120M_90G.raw	Raw
	PLK193_OE480_231030_BC_CB_dpi3_3_2-3uL_DIA-FAIMS_120M_90G.raw	Raw
	PLK193_OE480_231030_BC_CB_dpi5_1_3-2uL_DIA-FAIMS_120M_90G.raw	Raw
	PLK193_OE480_231030_BC_CB_dpi5_2_2-2uL_DIA-FAIMS_120M_90G.raw	Raw

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Publications

The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa.

Sheikh Shaghayegh S Turpin Knotková Barbora B Benz Corinna C Eliáš Marek M Bílý Tomáš T Bondar Alexey A Tesařová Martina M Stříbrná Eva E Heller Jiří J Meinecke Michael M Hashimi Hassan H

Molecular biology and evolution 20251001 11

Cristae enclose respiratory chain complexes, making them the bioenergetic subcompartments of mitochondria. The Mitochondrial contact site and Cristae Organizing System (MICOS) complex is among the inducers of membrane curvature needed for crista formation. Resembling the respiratory chain complexes, MICOS is organized around a core protein, the mitofilin-domain bearing Mic60, that was inherited from the alphaproteobacterial progenitor of mitochondria. Extant alphaproteobacteria express Mic60 to ...[more]

PMID: 41208531

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