bims-mitdyn 2025-02-09 papers

Mitochondrion. 2025 Feb 03. pii: S1567-7249(25)00005-4. [Epub ahead of print] 102008

The unusual suspect: A novel role for intermediate filament proteins in mitochondrial morphology.

Irene M G M Hemel, Carlijn Steen, Simon L I J Denil, Gökhan Ertaylan, Martina Kutmon, Michiel Adriaens, Mike Gerards.

Mitochondrial dynamics is crucial for cellular homeostasis. However, not all proteins involved are known. Using a protein-protein interaction (PPI) approach, we identified ITPRIPL2 for involvement in mitochondrial dynamics. ITPRIPL2 co-localizes with intermediate filament protein vimentin, supported by protein simulations. ITPRIPL2 knockdown reveals mitochondrial elongation, disrupts vimentin processing, intermediate filament formation, and alters vimentin-related pathways. Interestingly, vimentin knockdown also leads to mitochondrial elongation. These findings highlight ITPRIPL2 as vimentin-associated protein essential for intermediate filament structure and suggest a role for intermediate filaments in mitochondrial morphology. Our study demonstrates that PPI analysis is a powerful approach for identifying novel mitochondrial dynamics proteins.

Keywords: Intermediate filaments; Mitochondria; Mitochondrial dynamics; Network analysis; Protein-protein interactions

DOI: https://doi.org/10.1016/j.mito.2025.102008

J Vis Exp. 2025 Jan 17.

Imaging and Quantifying Mitochondrial Morphology in C. elegans During Aging.

Juri Kim, Maxim Averbukh, Athena Alcala, Rebecca Aviles Barahona, Matthew Vega, Gilberto Garcia, Ryo Higuchi-Sanabria, Naibedya Dutta.

Mitochondria, important cellular organelles found in most eukaryotic cells, are major sites of energy production through aerobic respiration. Beyond this well-known role as the 'cellular powerhouse,' mitochondria are also involved in many other essential cellular processes, including the regulation of cellular metabolism, proliferation, immune signaling, and hormonal signaling. Deterioration in mitochondrial function during aging or under mitochondrial stress is often characterized by distinct changes in mitochondrial morphology and volume. The nematode C. elegans is an ideal model for studying these changes due to its transparent body and short lifespan, which facilitate live microscopy throughout its lifetime. However, even within the C. elegans field, numerous transgenic constructs and methods for mitochondrial imaging are available, each with its own limitations. Here, single-copy, matrix-localized GFP constructs are presented as a robust and reliable method for imaging mitochondrial morphology in C. elegans. This study specifically focuses on experimentally controllable factors to minimize errors and reduce variability between replicates and across studies when performing mitochondrial imaging during the aging process. Additionally, mitoMAPR is recommended as a robust method to quantify changes in mitochondrial morphology across tissue types during aging.

DOI: https://doi.org/10.3791/67610

Nat Commun. 2025 Feb 01. 16(1): 1258

Nutrient status alters developmental fates via a switch in mitochondrial homeodynamics.

Jie Zhang, Suning Liu, Yang Li, Guanfeng Xu, Huimin Deng, Kirst King-Jones, Sheng Li.

Steroid hormones are powerful endocrine regulators, but little is known about how environmental conditions modulate steroidogenesis to reprogram developmental fates. Here, we use the Drosophila prothoracic gland (PG) to investigate how a nutrient restriction checkpoint (NRC) ensures or blocks developmental progression and sexual maturation via regulating steroidogenesis. Extensive transcriptome analysis of the PG reveals that pre-NRC starvation significantly downregulates mitochondria-associated genes. Pre-NRC starvation reduces prothoracicotropic neuropeptide hormone signaling, insulin signaling, and TORC1 activity in PG cells, which prevent mitochondrial fragmentation and import of Disembodied, a key steroidogenic enzyme. Ultimately, pre-NRC starvation causes severe mitophagy and proteasome dysfunction, blocking steroidogenesis and metamorphosis. By contrast, post-NRC starvation does not impair mitochondrial homeostasis in PG cells but reduces sit expression and induces moderate autophagy to promote steroidogenesis, leading to precocious metamorphosis. This study constitutes a paradigm for exploring how steroid hormone levels are controlled in response to environmental stress during developmental checkpoints.

DOI: https://doi.org/10.1038/s41467-025-56528-z

Anal Chem. 2025 Feb 02.

Harnessing an MMP-Independent NIR Probe Unveiling the Different Mitochondrial Cristae Changes during Mitophagy and Ferroptosis under STED Microscopy.

Yangang Su, Wendong Jin, Jie Niu, Xingyu Lyu, Qiuhua Hao, Qing Lyu, Nan Sheng, Zhiqiang Liu, Xiaoqiang Yu.

Mitochondrial cristae remain dynamic structures in order to adapt various physiopathologic processes (e.g., mitophagy and ferroptosis); thus, visualizing and tracking different changes of cristae are crucial for a deeper understanding of these processes. Fluorescent probes that can realize long-term visualization of mitochondrial cristae under stimulated emission depletion (STED) microscopy are powerful tools for their in-depth research. However, there are few reports on such probes, and their constructions remain challenging. Here, we reported a robust squaraine probe (CSN) for visualizing and tracking the changes of mitochondrial cristae in various physiological and pathological processes using STED microscopy. The lipophilic unit of CSN enabled it to firmly immobilize in mitochondria via a hydrophobic interaction, which let the labeling ability of CSN independent of mitochondrial membrane potential (MMP). Using CSN, the mitochondrial cristae were clearly observed at a resolution of 52 nm under STED microscopy. Furthermore, CSN was successfully applied to track the destruction processes of mitochondrial cristae during autophagy and ferroptosis. Interestingly, we found that during mitophagy, mitochondria first underwent swelling and cristae rupture, and then partial vacuolization, and finally complete vacuolization, whereas during ferroptosis, mitochondria first underwent a gradual reduction in the number of cristae, and then partial fracture, and finally vacuolization. This work revealed the difference in mitochondrial cristae changes during mitophagy and ferroptosis, which provided insights into the two physiological and pathological processes. We believed that CSN could serve as a desirable tool to track cristae changes of intracellular activity processes.

DOI: https://doi.org/10.1021/acs.analchem.4c05544