bims-mitpro 2026-02-22 papers

Issue of 2026–02–22
three papers selected by
Andreas Kohler, Umeå University

Plant Cell Physiol. 2026 Feb 19. pii: pcag006. [Epub ahead of print]

Functional FTSH4 Complexes In Arabidopsis Mitochondria: A Megacomplex with SLP1 and SLP1-free Smaller Complexes.

Agata Maziak, Małgorzata Heidorn-Czarna, Bernadette Gehl-Väisänen, Urszula Kaźmierczak, Hanna Jańska.

The FTSH4 protease is a major component of the Arabidopsis mitochondrial protein quality control system. It has both a proteolytic and a chaperone-like activity and forms complexes anchored in the inner mitochondrial membrane. Here, we show that FTSH4 assembles into two distinct forms: a dominant high-molecular-weight megacomplex with stomatin-like protein 1 (SLP1), and smaller SLP1-free assemblies. In the slp1-1 mutant, the FTSH4-SLP1 megacomplex is absent, while the abundance of SLP1-free FTSH4 assemblies is nearly doubled. Despite this, slp1-1 maintains wild-type levels of FTSH4 substrates, TIM17-2 and NAD9, indicating that the SLP1-free assemblies retain proteolytic activity. Furthermore, slp1-1 mitochondria accumulate fewer detergent-resistant HSP23.6 aggregates under elevated temperature than ftsh4-1 and even wild-type. Consequently, the mitochondrial unfolded protein response reported in ftsh4-1 is not induced in slp1-1. Although slp1-1 plants display morphological changes previously associated with ftsh4-1, such as shorter inflorescence stems due to premature arrest of the shoot apical meristem, these are less pronounced. Taken together, the increased abundance of SLP1-free FTSH4 assemblies is sufficient to support general mitochondrial proteostasis, providing effective protection against heat-induced aggregation of mitochondrial proteins. In contrast, the FTSH4-SLP1 megacomplex more effectively fulfils the meristem-specific functions of FTSH4.

Keywords: Arabidopsis thaliana ; FTSH4 protease; SLP1; mitochondria; protein complexes; stomatin

DOI: https://doi.org/10.1093/pcp/pcag006

Autophagy Rep. 2026 ;5(1): 2627062

A New biosensor illuminates the driving force behind mitochondrial outer membrane rupture.

Wei-Hua Chu, Wei-Chung Chiang.

In PINK1 (PTEN induced kinase 1)/PRKN (Parkin)-mediated mitophagy, the rupture of the outer mitochondrial membrane (OMM) emerges as a crucial event required for efficient mitochondrial clearance. Mechanistically, OMM rupture exposes inner mitochondrial membrane (IMM) mitophagy receptors, facilitating subsequent autophagic removal. Despite the important role of OMM rupture in mitophagy, the underlying mechanism remains elusive and technically difficult to monitor. In a recent study, we developed a novel fluorescent biosensor to directly visualize OMM rupture. This technique enables temporal and spatial characterization of OMM rupture and provides a powerful platform to dissect the underlying mechanism. Using this tool, we revealed that VCP (valosin containing protein) and its recruitment factors are required for OMM rupture, suggesting that VCP-dependent remodeling of the OMM proteome primes the rupture of OMM during mitophagy. Abbreviations: ARIH1, Ariadne RBR E3 ubiquitin protein Ligase 1; AMFR, autocrine motility factor receptor; ANKRD13A, ankyrin repeat domain-containing protein 13 A; FUNDC1, FUN14 domain containing 1; OA, oligomycin and antimycin; CID, chemical-induced dimerization; IMM, nner mitochondrial membrane; LC3, microtubule-associated protein 1 light chain 3; MUL1, mitochondrial E3 ubiquitin protein ligase 1; NIX, BCL2 interacting protein 3 like; OMM, outer mitochondrial membrane; UBXN1, ubiquitin regulatory X domain-containing protein 1; UBXN6, ubiquitin regulatory X domain-containing protein 6; VCP, valosin-containing protein; WIPI2, WD repeat domain phosphoinositide interacting protein 2.

Keywords: Biosensor; Mitochondrial outer membrane rupture; Mitochondrial quality control; PINK1/Parkin-mediated mitophagy; VCP

DOI: https://doi.org/10.1080/27694127.2026.2627062

bioRxiv. 2026 Feb 12. pii: 2025.12.22.695711. [Epub ahead of print]

De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response.

Rui Yang, Kaiyuan Zheng, McGuire Metts, Yiluo Wang, Danyan Yin, Kevin P Li, Agnieszka A Prazmowska, David F Kashatus, Brian Kuhlman, Jie Yang.

Mitochondrial stress activates the integrated stress response (ISR) through the mitochondrial protein DELE1, which relays stress signals to the cytosolic kinase HRI to induce ATF4. Dysregulation of DELE1-mediated signaling has been implicated in pathological conditions, yet molecular strategies to modulate DELE1 remain unavailable. Here, we report de novo designed proteins that bind DELE1, block its oligomerization, and inhibit DELE1-mediated ISR activation. Several designs form stable complexes with DELE1 and disrupt its oligomerization in vitro while preserving DELE1's ability to bind HRI. In cells, these designs suppress ATF4 induction during mitochondrial stress and impair the recovery of elongated mitochondrial morphology following transient insult. Crystal structure analysis, structural modeling, and targeted mutagenesis confirm that the designed proteins engage a critical interface required for DELE1 oligomerization. These findings establish DELE1 as a druggable target and demonstrate that de novo designed proteins offer precise tools to modulate this pathway, laying groundwork for therapeutic development.

DOI: https://doi.org/10.64898/2025.12.22.695711