Cellular senescence links mitochondria-ER contacts and aging

Ziegler, Dorian V.; Martin, Nadine; Bernard, David

doi:10.1038/s42003-021-02840-5

Cited by 35 publications

(40 citation statements)

References 184 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disruption of MERCs has also been associated with Parkinson's disease (PD). Under normal conditions, the αsynuclein, Parkin and PTEN-induced kinase (PINK) proteins are concentrated in MAMs, while mutations in these proteins have been associated with disturbances of mitochondrial-ER communication (Ziegler et al, 2021a). Likewise, the absence of Parkin can explain a relative resistance to mitophagy in neurons, thus favoring the accumulation of dysfunctional mitochondria and neuronal damage (Kook et al, 2020;Lopez-Crisosto et al, 2021).…”

Section: Mitochondria-er Contacts and Their Relationship With Neurona...mentioning

confidence: 99%

The aging of ER-mitochondria communication: A journey from undifferentiated to aged cells

Morgado-Cáceres

Liabeuf

Calle

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The complex physiology of eukaryotic cells requires that a variety of subcellular organelles perform unique tasks, even though they form highly dynamic communication networks. In the case of the endoplasmic reticulum (ER) and mitochondria, their functional coupling relies on the physical interaction between their membranes, mediated by domains known as mitochondria-ER contacts (MERCs). MERCs act as shuttles for calcium and lipid transfer between organelles, and for the nucleation of other subcellular processes. Of note, mounting evidence shows that they are heterogeneous structures, which display divergent behaviors depending on the cell type. Furthermore, MERCs are plastic structures that remodel according to intra- and extracellular cues, thereby adjusting the function of both organelles to the cellular needs. In consonance with this notion, the malfunction of MERCs reportedly contributes to the development of several age-related disorders. Here, we integrate current literature to describe how MERCs change, starting from undifferentiated cells, and their transit through specialization, malignant transformation (i.e., dedifferentiation), and aging/senescence. Along this journey, we will review the function of MERCs and their relevance for pivotal cell types, such as stem and cancer cells, cardiac, skeletal, and smooth myocytes, neurons, leukocytes, and hepatocytes, which intervene in the progression of chronic diseases related to age.

show abstract

Section: Mitochondria-er Contacts and Their Relationship With Neurona...mentioning

confidence: 99%

The aging of ER-mitochondria communication: A journey from undifferentiated to aged cells

Morgado-Cáceres

Liabeuf

Calle

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…For example, mitochondrial fission is regulated by mito-LE/Lys contacts that are also positive for ER (Wong et al, 2018 ). Given the close interplay between MCSs, our aim here is to first provide a brief overview of MAM alterations in PD and AD [which has been reviewed elsewhere, see (Gómez-Suaga et al, 2018 ; Raeisossadati and Ferrari, 2020 ; Leal and Martins, 2021 ; Lim et al, 2021 ; Ray et al, 2021 ; Ziegler et al, 2021 )], to then focus on the more poorly characterized MCSs (for a graphical abstract, see Figures 2 , 3 , respectively).…”

Section: Mams In Pd and Admentioning

confidence: 99%

“…Over the past years, also the field of neurodegeneration research is becoming increasingly aware of the importance of inter-organellar communication in neuronal survival. Given that mitochondrial defects are a common feature to most neurodegenerative diseases (NDs), including Parkinson's (PD) and Alzheimer's (AD), most attention has been given to contacts involving mitochondria, specifically with the endoplasmic reticulum (ER) [for a detailed review, see (Gómez-Suaga et al, 2018 ; Raeisossadati and Ferrari, 2020 ; Leal and Martins, 2021 ; Lim et al, 2021 ; Ray et al, 2021 ; Ziegler et al, 2021 )]. However, more recent observations fail to reconcile different NDs-associated cellular mechanisms such as endolysosomal disruption, with sole impairments in ER-mitochondria contact sites (Petkovic et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites

et al. 2022

View full text Add to dashboard Cite

Neurodegenerative diseases (NDs) are generally considered proteinopathies but whereas this may initiate disease in familial cases, onset in sporadic diseases may originate from a gradually disrupted organellar homeostasis. Herein, endolysosomal abnormalities, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and altered lipid metabolism are commonly observed in early preclinical stages of major NDs, including Parkinson's disease (PD) and Alzheimer's disease (AD). Among the multitude of underlying defective molecular mechanisms that have been suggested in the past decades, dysregulation of inter-organellar communication through the so-called membrane contact sites (MCSs) is becoming increasingly apparent. Although MCSs exist between almost every other type of subcellular organelle, to date, most focus has been put on defective communication between the ER and mitochondria in NDs, given these compartments are critical in neuronal survival. Contributions of other MCSs, notably those with endolysosomes and lipid droplets are emerging, supported as well by genetic studies, identifying genes functionally involved in lysosomal homeostasis. In this review, we summarize the molecular identity of the organelle interactome in yeast and mammalian cells, and critically evaluate the evidence supporting the contribution of disturbed MCSs to the general disrupted inter-organellar homeostasis in NDs, taking PD and AD as major examples.

show abstract

“…Recently, MERCs have also been indicated as molecular platforms contributing to aging and age-related diseases via SASP signaling [ 182 ]. Indeed, alterations of MERCs quantity and quality with aging and related diseases have been reported [ 95 , 96 , 104 ].…”

Section: Mitochondrial Dyshomeostasis and Inflammation In Aging And R...mentioning

confidence: 99%

Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions

Picca

Guerra

Calvani

et al. 2022

Cells

View full text Add to dashboard Cite

Mitochondria are primarily involved in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. An immunostimulatory property of mitochondria has also been recognized which is deployed through the extracellular release of entire or portioned organelle and/or mitochondrial DNA (mtDNA) unloading. Dynamic homo- and heterotypic interactions involving mitochondria have been described. Each type of connection has functional implications that eventually optimize mitochondrial activity according to the bioenergetic demands of a specific cell/tissue. Inter-organelle communications may also serve as molecular platforms for the extracellular release of mitochondrial components and subsequent ignition of systemic inflammation. Age-related chronic inflammation (inflamm-aging) has been associated with mitochondrial dysfunction and increased extracellular release of mitochondrial components—in particular, cell-free mtDNA. The close relationship between mitochondrial dysfunction and cellular senescence further supports the central role of mitochondria in the aging process and its related conditions. Here, we provide an overview of (1) the mitochondrial genetic system and the potential routes for generating and releasing mtDNA intermediates; (2) the pro-inflammatory pathways elicited by circulating mtDNA; (3) the participation of inter-organelle contacts to mtDNA homeostasis; and (4) the link of these processes with senescence and age-associated conditions.

show abstract

Cellular senescence links mitochondria-ER contacts and aging

Cited by 35 publications

References 184 publications

The aging of ER-mitochondria communication: A journey from undifferentiated to aged cells

The aging of ER-mitochondria communication: A journey from undifferentiated to aged cells

Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites

Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions

Contact Info

Product

Resources

About