Nucleus to Mitochondria: Lost in Transcription, Found in Translation

St-Pierre, Julie; Topisirović, Ivan

doi:10.1016/j.devcel.2016.06.003

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…These results imply that both RPs and PPR proteins are effectors in iMUCH evoked proteostatic response. Therefore, our findings provide a framework to better understand how a regulatory network that combines transcriptional and post transcriptional mechanisms to coordinate nuclear-and mitochondrial-encoded gene expression for maintaining cellular homeostasis 63,64 .…”

Section: Discussionmentioning

confidence: 93%

Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Zhang

Bao

et al. 2022

Preprint

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Mitochondrial Ca2+ (mtCa2+) homeostasis is essential to mitochondrial functions. However, how mtCa2+ homeostasis is achieved and the consequences of impaired mtCa2+ homeostasis in plants is poorly understood. Here, we demonstrate a critical role for mitochondrial Ca2+ uniporter (MCU) in the control of mtCa2+ uptake for mtCa2+ homeostasis in planta by characterizing MCU mutants and overexpressed plants. Impaired MCU-controlled mtCa2+ homeostasis (iMUCH) in gain-of-function and loss-of-function MCU plants causes the misregulation of mitochondrial gene expression that triggers mitonuclear protein imbalance. Transcriptome integrated with proteomics analysis reveal activation of multiple compartmental UPR gene expression and decrease of cytosolic translation with selective repression of ribosome and RNA modification protein synthesis upon iMUCH. Intriguingly, TOR signalling is not involved in cytosolic translational response to iMUCH, but the reduction of eIF2alpha; phosphorylation is evident under iMUCH induced mitochondrial stress. Thus, our study unveils the essential functions of MCU proteins for mtCa2+ homeostasis, and the involvement of MCU-controlled mtCa2+ homeostasis in mitochondrial stress dependent regulation of protein synthesis for cellular proteostasis that is connected to plant growth and stress resistance.

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Section: Discussionmentioning

confidence: 93%

Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Zhang

Bao

et al. 2022

Preprint

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“…Several nuclear messengers that encode mitochondrial proteins including complex I and II subunits are translated at the mitochondria periphery in yeast, plant and animal cells. Localized translation can enable co-translational import and assembly, thus helping the biogenesis of multi-subunit complexes (Gehrke et al, 2015; Schatton & Rugarli, 2018; St-Pierre & Topisirovic, 2016; Vincent et al, 2017; Wilk et al, 2016; Williams et al, 2014; Wu et al, 2018). Relevantly, biogenesis of succinate dehydrogenase complex involves a strict co-translational control with the participation of multiple co-factors, and mutations in assembly factors lead to serious mitochondrial defects (reviewed in (Moosavi et al, 2019)).…”

Section: Discussionmentioning

confidence: 99%

Smaug membraneless organelles regulate mitochondrial function

Fernández-Alvarez

Thomas

Pascual

et al. 2020

Preprint

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Smaug is a conserved translational repressor that recognizes specific RNA motifs in a large number of mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs have been shown to form membraneless organelles (MLOs) in several organisms and cell types. Using single-molecule FISH we show here that SDHB and UQCRC1 mRNAs associate with Smaug1 MLOs in the human cell line U2OS. Simultaneous loss of function of Smaug1 and Smaug2 affects both mitochondrial respiration and mitochondrial network morphology. Deletion of specific Smaug1 protein regions resulted in impaired MLO formation that correlates with mitochondrial defects. In addition, rotenone but not the respiratory chain uncoupling agent CCCP rapidly induces Smaug1 MLO dissolution. Finally, metformin elicits a similar effect on Smaug1 MLOs and provokes the release of bounded mRNAs. We propose that mitochondrial activity affects Smaug1 MLO dynamics, thus allowing for regulation of nuclear mRNAs that encode key mitochondrial proteins.

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“…The chemical energy produced by oxidative phosphorylation in the mitochondria is stored in adenosine triphosphate (ATP) (2). The energy generated by mitochondria are crucial for various cellular activities, including gene transcription, protein synthesis, cell differentiation and growth, mitosis and meiosis (3)(4)(5)(6)(7). Mitochondria also provide a platform for metabolic pathways, including tricarboxylic acid cycle, oxidation, and lipid synthesis (8).…”

Section: Introductionmentioning

confidence: 99%

ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis and meiosis

Guo

Xiao

et al. 2022

Preprint

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Caseinolytic protease proteolytic subunit (ClpP) and caseinolytic protease X (ClpX) are mitochondrial matrix peptidases that activate mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis in the mitochondria. However, the role of ClpP and ClpX in spermatogenesis remains largely unknown. In this study, we demonstrated the importance of ClpP/ClpX for meiosis and spermatogenesis with two conditional knockout (cKO) mouse models. We found that ClpP/ClpX deficiency reduced mitochondrial functions and quantity in spermatocytes, affected energy supply during meiosis and attenuated zygotene-pachytene transformation of the male germ cells. The affected spermatocytes exhibited disorder of chromosome synapsis and cross-over events. Their telomeres failed to attach to the nuclear envelop, which was associated with failure of alpha-tubulin formation in the ClpP/ClpX cKO spermatocytes. The dysregulated spermatocytes finally underwent apoptosis resulting in decreased testicular size and vacuolar structures within the seminiferous tubules. Both transcriptome analysis and m6A-methylation sequencing analysis highlighted dysregulation of metabolic pathways including the mTOR signaling in the isolated spermatocytes. We confirmed over-activation of the mTORC1 pathway with increased expression of phosphorylated S6 and 4EBP after deletion of ClpP/ClpX in spermatocytes. Long-term inhibition of the mTORC1 signaling via rapamycin treatment in vivo partially rescue spermatogenesis in the seminiferous tubules with much less apoptotic germ cells and formation of late stage of meiotic germ cells, such as round spermatids and elongated spermatozoon. The data reveal the novel roles of ClpP and ClpX in regulating meiosis and spermatogenesis.

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Nucleus to Mitochondria: Lost in Transcription, Found in Translation

Cited by 5 publications

References 13 publications

Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Smaug membraneless organelles regulate mitochondrial function

ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis and meiosis

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Nucleus to Mitochondria: Lost in Transcription, Found in Translation

Cited by 5 publications

References 13 publications

Perturbation of mitochondrial Ca2+ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Perturbation of mitochondrial Ca2+ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Smaug membraneless organelles regulate mitochondrial function

ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis and meiosis

Contact Info

Product

Resources

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Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis