Mitochondria-ER contact sites expand during mitosis

Yu, Fang; Courjaret, Raphael; Assaf, Lama; Elmi, Asha; Hammad, Ayat; Fisher, Melanie; Terasaki, Mark; Machaca, Khaled

doi:10.1016/j.isci.2024.109379

Cited by 5 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine whether purified mitochondria remained intact, we examined the pellets from the immunoprecipitations using transmission electron microscopy and found that the majority of immuno-isolated membranous structures were indeed mitochondria with well-preserved ultrastructure ( Figure 2C ). Additional membranous structures were also observed, likely representing the endoplasmic reticulum, which is known to establish contact sites with mitochondria 44, 45 .…”

Section: Resultsmentioning

confidence: 99%

Compartmental Differences in the Retinal Ganglion Cell Mitochondrial Proteome

Lewis,

Skiba,

Hao

et al. 2024

Preprint

View full text Add to dashboard Cite

Among neurons, retinal ganglion cells (RGCs) are uniquely sensitive to mitochondrial dysfunction. The RGC is highly polarized, with a somatodendritic compartment in the inner retina and an axonal compartment projecting to targets in the brain. The drastically dissimilar functions of these compartments implies that mitochondria face different bioenergetic and other physiological demands. We hypothesized that compartmental differences in mitochondrial biology would be reflected by disparities in mitochondrial protein composition. Here, we describe a protocol to isolate intact mitochondria separately from mouse RGC somatodendritic and axonal compartments by immunoprecipitating labeled mitochondria from RGC MitoTag mice. Using mass spectrometry, 471 and 357 proteins were identified in RGC somatodendritic and axonal mitochondrial immunoprecipitates, respectively. We identified 10 mitochondrial proteins exclusively in the somatodendritic compartment and 19 enriched ≥2-fold there, while 3 proteins were exclusively identified and 18 enriched in the axonal compartment. Our observation of compartment-specific enrichment of mitochondrial proteins was validated through immunofluorescence analysis of the localization and relative abundance of superoxide dismutase (SOD2), sideroflexin-3 (SFXN3) and trifunctional enzyme subunit alpha (HADHA) in retina and optic nerve specimens. The identified compartmental differences in RGC mitochondrial composition may provide promising leads for uncovering physiologically relevant pathways amenable to therapeutic intervention for optic neuropathies.

show abstract

Section: Resultsmentioning

confidence: 99%

Compartmental Differences in the Retinal Ganglion Cell Mitochondrial Proteome

Lewis,

Skiba,

Hao

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

ERMCS Ca2+ transmission fuels cell division

Madesh,

Vishnu,

Tomar

2024

Trends in Cell Biology

View full text Add to dashboard Cite

Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation, and cell cycle progression

Shannon,

Raymond,

Palmer

et al. 2024

Preprint

View full text Add to dashboard Cite

Subcellular mitochondrial positioning in cells is necessary for localized energy and signaling requirements. Mitochondria are strategically trafficked throughout the cytoplasm via the actin cytoskeleton, microtubule motor proteins, and adaptor proteins. Miro1, an outer mitochondrial membrane adaptor protein, is necessary for attachment of mitochondria to microtubule motor proteins for trafficking. Previous work showed when Miro1 is deleted (Miro1-/-) from mouse embryonic fibroblasts (MEFs), the mitochondria become sequestered to the perinuclear space, disrupting subcellular energy and reactive oxygen species gradients. Here, we show that Miro1-/- MEFs grow slower compared to Miro1+/+ and Miro1-/- MEFs stably re-expressing the Myc-Miro1 plasmid. Miro1-/- MEFs have a have a cell cycle defect with decreased percentage of cells in G1 and increased cells in the S phase of the cell cycle. We conducted the first ever RNA sequencing experiment dependent upon Miro1 expression and found differential expression in cell proliferation and migration genes upon deletion of Miro1, including the MAP Kinase signaling pathway. We find that ERK1/2 phosphorylation is elevated both spatially (cytoplasm and nucleus) and temporally following serum stimulation in Miro1-/- MEFs. We investigated the expression levels and oxidation of the Dual Specificity Phosphatases (DUSP1-6), ERK1/2 target phosphatases. We found no differences in DUSP1-6 expression and oxidation under asynchronous and synchronized cells. Lastly, we evaluated the oxidation status of ERK1/2 and found an increase in ERK1/2 oxidation in the Miro1-/- MEFs compared to Miro1+/+ and Myc-Miro1. These data highlight transcriptional control based off Miro1 expression and demonstrate the highly dynamic regulation of ERK1/2 upon deletion of Miro1 that may support the observed cell cycle and proliferation defects.

show abstract

Mitochondria-ER contact sites expand during mitosis

Cited by 5 publications

References 51 publications

Compartmental Differences in the Retinal Ganglion Cell Mitochondrial Proteome

Compartmental Differences in the Retinal Ganglion Cell Mitochondrial Proteome

ERMCS Ca2+ transmission fuels cell division

Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation, and cell cycle progression

Contact Info

Product

Resources

About