Live cell microscopy of mitochondria-lysosome contact site formation and tethering dynamics

Belton, Tayler B.; Leisten, Eric D; Cisneros, Jasmine; Wong, Yvette C.

doi:10.1016/j.xpro.2022.101262

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…Inter-lysosomal contacts and mitochondria–lysosome contacts imaged in live cells were categorized as those that showed the two organelles in close proximity (<0.1 µm) for >10 s in time-lapse images ( Belton et al, 2022 ; Wong et al, 2018 ). The percentage of lysosomes in contacts were quantified as the percentage of lysosomes that formed contacts with mitochondria or other lysosomes in a region of interest per cell.…”

Section: Methodsmentioning

confidence: 99%

Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics

Wong

Kim

Cisneros

et al. 2022

Journal of Cell Biology

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Lysosomes are highly dynamic organelles implicated in multiple diseases. Using live super-resolution microscopy, we found that lysosomal tethering events rarely undergo lysosomal fusion, but rather untether over time to reorganize the lysosomal network. Inter-lysosomal untethering events are driven by a mitochondrial Mid51/Fis1 complex that undergoes coupled oligomerization on the outer mitochondrial membrane. Importantly, Fis1 oligomerization mediates TBC1D15 (Rab7-GAP) mitochondrial recruitment to drive inter-lysosomal untethering via Rab7 GTP hydrolysis. Moreover, inhibiting Fis1 oligomerization by either mutant Fis1 or a Mid51 oligomerization mutant potentially associated with Parkinson’s disease prevents lysosomal untethering events, resulting in misregulated lysosomal network dynamics. In contrast, dominant optic atrophy–linked mutant Mid51, which does not inhibit Mid51/Fis1 coupled oligomerization, does not disrupt downstream lysosomal dynamics. As Fis1 conversely also regulates Mid51 oligomerization, our work further highlights an oligomeric Mid51/Fis1 mitochondrial complex that mechanistically couples together both Drp1 and Rab7 GTP hydrolysis machinery at mitochondria–lysosome contact sites. These findings have significant implications for organelle networks in cellular homeostasis and human disease.

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Section: Methodsmentioning

confidence: 99%

Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics

Wong

Kim

Cisneros

et al. 2022

Journal of Cell Biology

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“…Mitochondria fractions were prepared as previously described [28,[34][35][36]. The activity of ETC complexes and citrate synthase was measured in mitochondrial extracts, as previously described [37].…”

Section: Etc Complexes and Citrate Synthase Activity Assaymentioning

confidence: 99%

Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma

et al. 2023

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Median overall survival is very low in patients with glioblastoma (GBM), largely because these tumors become resistant to therapy. Recently, we found that a decrease in the cytosolic labile iron pool underlies the acquisition of radioresistance. Both cytosolic and mitochondrial iron are important for regulating ROS production, which largely facilitates tumor progression and response to therapy. Here, we investigated the role of the mitochondrial iron transporters mitoferrin-1 (MFRN1) and mitoferrin-2 (MFRN2) in GBM progression. Analysis of The Cancer Genome Atlas database revealed upregulation of MFRN1 mRNA and downregulation of MFRN2 mRNA in GBM tumor tissue compared with non-GBM tissue, yet only the tumor expression level of MFRN1 mRNA negatively correlated with overall survival in patients. Overexpression of MFRN1 in glioma cells significantly increased the level of mitochondrial iron, enhanced the proliferation rate and anchorage-independent growth of these cells, and significantly decreased mouse survival in an orthotopic model of glioma. Finally, MFRN1 overexpression stimulated the upregulation of glutathione, which protected glioma cells from 4-hydroxynonenal-induced protein damage. Overall, these results demonstrate a mechanistic link between MFRN1-mediated mitochondrial iron metabolism and GBM progression. Manipulation of MFRN1 may provide a new therapeutic strategy for improving clinical outcomes in patients with GBM.

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Mitochondria-Associated Organelle Crosstalk in Myocardial Ischemia/Reperfusion Injury

Yao,

Xie,

et al. 2024

J. of Cardiovasc. Trans. Res.

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Live cell microscopy of mitochondria-lysosome contact site formation and tethering dynamics

Cited by 5 publications

References 8 publications

Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics

Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics

Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma

Mitochondria-Associated Organelle Crosstalk in Myocardial Ischemia/Reperfusion Injury

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