Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes

Raffaello, Anna; Mammucari, Cristina; Gherardi, Gaia; Meneghesso, Gaudenzio

doi:10.1016/j.tibs.2016.09.001

Cited by 403 publications

(348 citation statements)

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“…Furthermore, it is now clear that mitochondria interact with other organelles, both through physical contact sites and through signaling pathways34. The interaction between mitochondria and the endoplasmic reticulum (ER) provides pivotal examples of both: the mitochondrial-ER contact sites have been extensively studied and are known to be key players in cellular calcium homeostasis5, while mitochondrial dysfunction has also been shown to trigger ER stress6.…”

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confidence: 99%

Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis

Fernández-Mosquera

Diogo²,

Yambire³

et al. 2017

Sci Rep

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Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial signaling affects other organelles, particularly lysosomes. Here, we demonstrate that mitochondrial respiratory chain (RC) impairments elicit a stress signaling pathway that regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, the effect of mitochondrial stress over lysosomal biogenesis depends on the timeframe of the stress elicited: while RC inhibition with rotenone or uncoupling with CCCP initially triggers lysosomal biogenesis, the effect peaks after few hours and returns to baseline. Long-term RC inhibition by long-term treatment with rotenone, or patient mutations in fibroblasts and in a mouse model result in repression of lysosomal biogenesis. The induction of lysosomal biogenesis by short-term mitochondrial stress is dependent on TFEB and MITF, requires AMPK signaling and is independent of calcineurin signaling. These results reveal an integrated view of how mitochondrial signaling affects lysosomes, which is essential to fully comprehend the consequences of mitochondrial malfunction, particularly in the context of mitochondrial diseases.

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mentioning

confidence: 99%

Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis

Fernández-Mosquera

Diogo²,

Yambire³

et al. 2017

Sci Rep

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“…12, 2017; epidemiological characteristics of SZ obviously increase the risk of spurious associations caused by subtle admixture and 2GLD. However, it does not per se refute the mitochondrial pathogenic paradigm 34 where variation in mitochondrial function, believed to interfere with ATP production 35,36 , inflammation and signaling 37,38 as well as Ca 2+ -homeostasis 39 , and apoptosis 38 , is considered to be of paramount importance for development of disease. Several neuroanatomical postmortem findings in SZ brains indicate perturbed mitochondrial function 40 , but such findings are difficult to distinguish from changes caused by drug treatment.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Hagen

Gonçalves

Hedley

et al. 2017

Preprint

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Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. A reanalysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 normal Danes and 2,538 schizophrenia patients, revealed marked inter-allelic differences in haplogroup affiliation and nuclear ancestry, genogeophraphic affinity (GGA). This bi-genomic linkage disequilibrium (2GLD) could entail population stratification. Only two mitochondrial SNPs, m.15043A and m.15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/149070 doi: bioRxiv preprint first posted online 3 Genetic variants in mitochondrial DNA (mtDNA) -and in nuclear genes coding for mitochondrial function -have been associated with disease 1-3 . More than 300 variants 4,5 in mtDNA and genes involved in mitochondrial function 6 have been reported to cause mitochondrial disease which is clinically characterised by complex metabolic, neurological, muscular and psychiatric symptoms 7,8 .SNPs in mtDNA and mitochondrial haplogroups (mtDNA hgs), which are evolutionarily fixed SNP sets with a characteristic geographical distribution, have been proposed as potential disease modifiers 8 . This has been reported in neurological degenerative diseases such as Alzheimer's disease 9-12 and Parkinson's disease 12-14 , metabolic diseases and cancers 15 , as well as psychiatric diseases, notably schizophrenia (SZ) and bipolar disease [16][17][18] .Association studies of mtDNA variants and disease have been difficult to replicate 8 . However, the definition of a methodological paradigm for association studies with mtDNA variants 19 implicitly assumes that mtDNA variants are independent of the nuclear genome. In a recent Danish study on mtDNA haplogroups and their nuclear ancestry or nuclear genogeographical affinity (GGA), we demonstrated a marked difference in nuclear ancestry between individual haplogroups 20 . This means that mtDNA hgs entail population stratification also at the level of gDNA. The effect of such a stratification on disease association, will depend on the admixture structure of the particular population, the population history, epidemiology and genetic epidemiology of the disease, as well as the number of persons included in the study. The extensive fine-scale heterogeneity of gDNA and significant admixture documented in the UK 21 and Europe 22 further increase the risk of spurious false positive associations, if the mtDNA/gDNA interaction is not corrected phenomenon for in association studies.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The co...

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“…Progress has been made in identifying connections and mapping numerous networks, and this information has guided our appreciation that there are sub-networks that form discrete functional units within any network. The organelles (mitochondria, nuclei, lysosomes, endoplasmic reticulum, Golgi) are prime examples of such functional units that need to perform specific tasks but also to be fully integrated with, and responding and reacting to, the activity of other sub-systems (Butow and Avadhani, 2004; Eisenberg-Bord et al, 2016; Raffaello et al, 2016). Thus, while originally considered to be autonomous within the confines of the cell (Wilson, 1928), organelles, compartments and structures such as peroxisomes, lipid droplets, and the plasma membrane are now appreciated as sub-networks within cells whose activities need to be fully integrated (Costanzo et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The Upsides and Downsides of Organelle Interconnectivity

Gottschling

Nyström

2017

Cell

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Interconnectivity and feedback control are hallmarks of biological systems. This includes communication between organelles, which allows them to function and adapt to changing cellular environments. While the specific mechanisms for all communications remain opaque, unraveling the wiring of organelle networks is critical to understand how biological systems are built and why they might collapse, as occurs in aging. A comprehensive understanding of all the routes involved in inter-organelle communication is still lacking but important themes are beginning to emerge, primarily in budding yeast. These routes are reviewed here in the context of sub-system proteostasis and Complex Adaptive Systems theory.

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Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes

Cited by 403 publications

References 115 publications

Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis

Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

The Upsides and Downsides of Organelle Interconnectivity

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