The cell-type specificity of mitochondrial dynamics

Kuznetsov, Andrey V.; Hermann, Michael; Saks, Valdur; Hengster, Paul; Margreiter, Raimund

doi:10.1016/j.biocel.2009.03.007

Cited by 146 publications

(110 citation statements)

References 132 publications

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“…Whereas a cell-type dependent regulation of mitochondrial morphology is well documented and usually linked to cell-type-specific functions and physiological energy demands. 82 Only 2 in vivo studies in rat report a gender-associated tissue difference in total autophagy, but not in mitophagy. 83,84 The cell lines used in this investigation are cybrids obtained from immortalized cells: respectively from adenocarcinoma-A549 23 and from rhabdomyosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

et al. 2016

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Pathological mutations in the mitochondrial DNA (mtDNA) produce a diverse range of tissue-specific diseases and the proportion of mutant mitochondrial DNA can increase or decrease with time via segregation, dependent on the cell or tissue type. Previously we found that adenocarcinoma (A549.B2) cells favored wild-type (WT) mtDNA, whereas rhabdomyosarcoma (RD.Myo) cells favored mutant (m3243G) mtDNA. Mitochondrial quality control (mtQC) can purge the cells of dysfunctional mitochondria via mitochondrial dynamics and mitophagy and appears to offer the perfect solution to the human diseases caused by mutant mtDNA. In A549.B2 and RD.Myo cybrids, with various mutant mtDNA levels, mtQC was explored together with macroautophagy/autophagy and bioenergetic profile. The 2 types of tumor-derived cell lines differed in bioenergetic profile and mitophagy, but not in autophagy. A549.B2 cybrids displayed upregulation of mitophagy, increased mtDNA removal, mitochondrial fragmentation and mitochondrial depolarization on incubation with oligomycin, parameters that correlated with mutant load. Conversely, heteroplasmic RD.Myo lines had lower mitophagic markers that negatively correlated with mutant load, combined with a fully polarized and highly fused mitochondrial network. These findings indicate that pathological mutant mitochondrial DNA can modulate mitochondrial dynamics and mitophagy in a cell-type dependent manner and thereby offer an explanation for the persistence and accumulation of deleterious variants.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

et al. 2016

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“…6C,D). Hence, mAKAP-RFP-CAAX expression strongly reduced mitochondrial motility to stochastically determined small-scale movements, whereas no directed long-distance movements (Kuznetsov et al, 2009;Saunter et al, 2009) could be observed (Fig. 7A).…”

Section: +mentioning

confidence: 94%

“…Our data presented herein show that expression of mAKAP-RFP-CAAX localized mitochondria to the plasma membrane. Hence mAKAP-RFP-CAAX expression yielded strong attenuation of oriented longdistance movements while the stochastic small-scale motility (Saunter et al, 2009) appeared to be unaffected, thus, indicating the lack of motor-protein-dependent movements but not of mitochondrial movement occurring by Brownian diffusion (Kuznetsov et al, 2009;Saunter et al, 2009). Our findings that the expression of mAKAP-RFP-CAAX results in a partial functional uncoupling of mitochondria from the ER is indicated by an attenuated mitochondrial Ca 2+ elevation upon ER Ca 2+ release (despite unchanged ER Ca 2+ release) as well as by the deceleration of the rate of Ca 2+ transfer from the ER to the mitochondria.…”

Section: +mentioning

confidence: 96%

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Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry

Naghdi

Waldeck-Weiermair

Fertschai

et al. 2010

Journal of Cell Science

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SummaryStore-operated Ca 2+ entry (SOCE) is established by formation of subplasmalemmal clusters of the endoplasmic reticulum (ER) protein, stromal interacting molecule 1 (STIM1) upon ER Ca 2+ depletion. Thereby, STIM1 couples to plasma membrane channels such as Orai1. Thus, a close proximity of ER domains to the plasma membrane is a prerequisite for SOCE activation, challenging the concept of local Ca 2+ buffering by mitochondria as being essential for SOCE. This study assesses the impact of mitochondrial Ca 2+ handling and motility on STIM1-Orai1-dependent SOCE. High-resolution microscopy showed only 10% of subplasmalemmal STIM1 clusters to be colocalized with mitochondria. Impairments of mitochondrial Ca 2+ handling by inhibition of mitochondrial Na + -Ca 2+ exchanger (NCX mito ) or depolarization only partially suppressed Ca 2+ entry in cells overexpressing STIM1-Orai1. However, SOCE was completely abolished when both NCX mito was inhibited and the inner mitochondrial membrane was depolarized, in STIM1-and Orai1-overexpressing cells. Immobilization of mitochondria by expression of mAKAP-RFP-CAAX, a construct that physically links mitochondria to the plasma membrane, affected the Ca 2+ handling of the organelles but not the activity of SOCE. Our observations indicate that mitochondrial Ca 2+ uptake, including reversal of NCX mito , is fundamental for STIM1-Orai1-dependent SOCE, whereas the proximity of mitochondria to STIM1-Orai1 SOCE units and their motility is not required.

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“…This plasticity of mitochondria ensures that they are able to respond to different cellular cues, which is potentially important for their numerous functions. In different cell types, mitochondria adopt varying morphologies (Kuznetsov et al 2009). For example, in cultured fibroblasts mitochondria form extensive reticular networks, whereas in neuronal cells, mitochondria can be found enriched at areas of high-energy demand, including presynaptic termini, axon initial segments, and growth cones.…”

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confidence: 99%

Quality Control of Mitochondrial Proteostasis

Baker

Tatsuta²,

Langer

2011

Cold Spring Harbor Perspectives in Biology

230

193

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A decline in mitochondrial activity has been associated with aging and is a hallmark of many neurological diseases. Surveillance mechanisms acting at the molecular, organellar, and cellular level monitor mitochondrial integrity and ensure the maintenance of mitochondrial proteostasis. Here we will review the central role of mitochondrial chaperones and proteases, the cytosolic ubiquitin-proteasome system, and the mitochondrial unfolded response in this interconnected quality control network, highlighting the dual function of some proteases in protein quality control within the organelle and for the regulation of mitochondrial fusion and mitophagy.

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The cell-type specificity of mitochondrial dynamics

Cited by 146 publications

References 132 publications

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry

Quality Control of Mitochondrial Proteostasis

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