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Article ; Online: Mitochondrial apoptosis: killing cancer using the enemy within.

Lopez, J / Tait, S W G

2015 Volume 112, Issue 6, Page(s) 957–962

Abstract: Apoptotic cell death inhibits oncogenesis at multiple stages, ranging from transformation to metastasis. Consequently, in order for cancer to develop and progress, apoptosis must be inhibited. Cell death also plays major roles in cancer treatment, ... ...

Abstract	Apoptotic cell death inhibits oncogenesis at multiple stages, ranging from transformation to metastasis. Consequently, in order for cancer to develop and progress, apoptosis must be inhibited. Cell death also plays major roles in cancer treatment, serving as the main effector function of many anti-cancer therapies. In this review, we discuss the role of apoptosis in the development and treatment of cancer. Specifically, we focus upon the mitochondrial pathway of apoptosis-the most commonly deregulated form of cell death in cancer. In this process, mitochondrial outer membrane permeabilisation or MOMP represents the defining event that irrevocably commits a cell to die. We provide an overview of how this pathway is regulated by BCL-2 family proteins and describe ways in which cancer cells can block it. Finally, we discuss exciting new approaches aimed at specifically inducing mitochondrial apoptosis in cancer cells, outlining their potential pitfalls, while highlighting their considerable therapeutic promise.
MeSH term(s)	Animals ; Apoptosis/physiology ; Carcinogenesis/pathology ; Cell Membrane Permeability/physiology ; Humans ; Mitochondria/pathology ; Neoplasms/pathology ; Signal Transduction/physiology
Language	English
Publishing date	2015-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2015.85
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Article ; Online: Mitochondrial control of inflammation.

Marchi, Saverio / Guilbaud, Emma / Tait, Stephen W G / Yamazaki, Takahiro / Galluzzi, Lorenzo

Nature reviews. Immunology

2022 Volume 23, Issue 3, Page(s) 159–173

Abstract: Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent ... ...

Abstract	Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal of permeabilized mitochondria. However, when the homeostatic capacity of such systems is exceeded or when such systems are defective, inflammatory reactions elicited by mitochondria can become pathogenic and contribute to the aetiology of human disorders linked to autoreactivity. In addition, inefficient inflammatory pathways induced by mitochondrial DAMPs can be pathogenic as they enable the establishment or progression of infectious and neoplastic disorders. Here we discuss the molecular mechanisms through which mitochondria control inflammatory responses, the cellular pathways that are in place to control mitochondria-driven inflammation and the pathological consequences of dysregulated inflammatory reactions elicited by mitochondrial DAMPs.
MeSH term(s)	Humans ; Mitochondria/metabolism ; Inflammation/pathology ; Alarmins ; Neoplasms/pathology
Chemical Substances	Alarmins
Language	English
Publishing date	2022-07-25
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-022-00760-x
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis.

Science advances

2024 Volume 10, Issue 11, Page(s) eadk7329

Abstract: Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. ... ...

Abstract	Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed. In contrast, MAVS mediated a noncanonical signal resulting in a prominent increase in mitochondrial ROS levels, and increase in the BACH1/pNRF2 transcription factor ratio and GPX4 up-regulation, which was associated with a 50% decrease in intracellular glutathione levels. We conclude that siRNAs commonly sensitize to ferroptosis and may severely compromise the conclusions drawn from silencing approaches in biomedical research. Finally, as ferroptosis contributes to a variety of pathophysiological processes, we cannot exclude side effects in human siRNA-based therapeutical concepts that should be clinically tested.
MeSH term(s)	Humans ; Signal Transduction ; RNA, Small Interfering/genetics ; Ferroptosis/genetics ; Up-Regulation ; Transcription Factors/metabolism
Chemical Substances	RNA, Small Interfering ; Transcription Factors
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adk7329
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Article ; Online: Association between preoperative ambulatory heart rate and postoperative myocardial injury: a retrospective cohort study.

Ladha, K S / Beattie, W S / Tait, G / Wijeysundera, D N

British journal of anaesthesia

2018 Volume 121, Issue 4, Page(s) 722–729

Abstract: Background: Resting heart rate is well established as a predictor of morbidity and mortality in the general population. However, the relationship between preoperative heart rate and perioperative outcomes, specifically myocardial injury, is unclear.: ... ...

Abstract	Background: Resting heart rate is well established as a predictor of morbidity and mortality in the general population. However, the relationship between preoperative heart rate and perioperative outcomes, specifically myocardial injury, is unclear. Methods: This retrospective cohort study included patients undergoing elective major non-cardiac surgery from 2008 to 2014 at a multisite healthcare system. The exposure was ambulatory heart rate measured during the outpatient preoperative clinic visit, whereas the outcome of interest was myocardial injury (peak postoperative troponin I concentration >30 ng L Results: The cohort included 41 140 patients, of whom 4857 (11.8%) experienced myocardial injury. Based on pre-specified heart categories thresholds, a heart rate ≥90 beats min Conclusions: This cohort study found that both very high preoperative heart rates, and possibly also very low heart rates, are associated with increased risk of myocardial injury. Whether heart rate is a modifiable risk factor, or rather simply a marker of underlying cardiac pathology, needs to be determined in further research.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathies/epidemiology ; Cohort Studies ; Female ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Models, Statistical ; Postoperative Complications/epidemiology ; Preoperative Period ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Troponin I/blood ; Young Adult
Chemical Substances	Troponin I
Language	English
Publishing date	2018-08-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2018.06.016
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Article ; Online: Evaluation of validity of the STOP-BANG questionnaire in major elective noncardiac surgery.

Sankar, A / Beattie, W S / Tait, G / Wijeysundera, D N

British journal of anaesthesia

2018 Volume 122, Issue 2, Page(s) 255–262

Abstract: Background: The STOP-BANG questionnaire screens for obstructive sleep apnoea (OSA) in surgical patients. In prior research, the association of STOP-BANG scores with comorbidities and outcomes was inconsistent. The objective of this study was to evaluate ...

Abstract	Background: The STOP-BANG questionnaire screens for obstructive sleep apnoea (OSA) in surgical patients. In prior research, the association of STOP-BANG scores with comorbidities and outcomes was inconsistent. The objective of this study was to evaluate the validity of the STOP-BANG score. Methods: We conducted a retrospective cohort study of patients undergoing major elective noncardiac surgery at the University Health Network (Toronto, ON, Canada) between 2011 and 2015. Cross-sectional construct validity was evaluated based on proportions with diagnosed OSA across STOP-BANG strata. Concurrent construct validity was assessed based on the correlation of STOP-BANG with ASA Physical Status (ASA-PS), the Revised Cardiac Risk Index, and the Charlson Comorbidity Index. Predictive validity was assessed based on the adjusted associations of STOP-BANG risk with 30-day mortality (logistic regression), cardiac complications (logistic regression), and length-of-stay (negative binomial regression). Results: Of 26 068 patients in the cohort, 58% were in the low-risk STOP-BANG stratum, 23% in the intermediate-risk stratum, and 19% in the high-risk stratum. The proportion with previously diagnosed OSA was 4% (n=615) in the low-risk stratum, 12% (n=740) in the intermediate-risk stratum, and 44% (n=2142) in the high-risk stratum. The correlations of STOP-BANG with ASA-PS (Spearman ρ=0.28), Revised Cardiac Risk Index (ρ=0.24), and Charlson Comorbidity Index (ρ=0.10) were weak, albeit statistically significant (P<0.001). After risk-adjustment, STOP-BANG risk strata were not associated with 30-day mortality, cardiac complications, or length-of-stay. Conclusions: The STOP-BANG questionnaire has modest construct validity but did not predict postoperative mortality, hospital length-of-stay, or cardiac complications.
MeSH term(s)	Aged ; Cohort Studies ; Comorbidity ; Cross-Sectional Studies ; Elective Surgical Procedures/methods ; Elective Surgical Procedures/mortality ; Female ; Heart Diseases/epidemiology ; Humans ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications/epidemiology ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/diagnosis ; Surveys and Questionnaires
Language	English
Publishing date	2018-12-11
Publishing country	England
Document type	Journal Article ; Validation Studies
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2018.10.059
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Article ; Online: Mitochondrial dynamics regulate genome stability via control of caspase-dependent DNA damage.

Cao, Kai / Riley, Joel S / Heilig, Rosalie / Montes-Gómez, Alfredo E / Vringer, Esmee / Berthenet, Kevin / Cloix, Catherine / Elmasry, Yassmin / Spiller, David G / Ichim, Gabriel / Campbell, Kirsteen J / Gilmore, Andrew P / Tait, Stephen W G

Developmental cell

2022 Volume 57, Issue 10, Page(s) 1211–1225.e6

Abstract: Mitochondrial dysfunction is interconnected with cancer. Nevertheless, how defective mitochondria promote cancer is poorly understood. We find that mitochondrial dysfunction promotes DNA damage under conditions of increased apoptotic priming. Underlying ... ...

Abstract	Mitochondrial dysfunction is interconnected with cancer. Nevertheless, how defective mitochondria promote cancer is poorly understood. We find that mitochondrial dysfunction promotes DNA damage under conditions of increased apoptotic priming. Underlying this process, we reveal a key role for mitochondrial dynamics in the regulation of DNA damage and genome instability. The ability of mitochondrial dynamics to regulate oncogenic DNA damage centers upon the control of minority mitochondrial outer membrane permeabilization (MOMP), a process that enables non-lethal caspase activation leading to DNA damage. Mitochondrial fusion suppresses minority MOMP and its associated DNA damage by enabling homogeneous mitochondrial expression of anti-apoptotic BCL-2 proteins. Finally, we find that mitochondrial dysfunction inhibits pro-apoptotic BAX retrotranslocation, causing BAX mitochondrial localization and thereby promoting minority MOMP. Unexpectedly, these data reveal oncogenic effects of mitochondrial dysfunction that are mediated via mitochondrial dynamics and caspase-dependent DNA damage.
MeSH term(s)	Apoptosis/genetics ; Apoptosis Regulatory Proteins/genetics ; Caspases/metabolism ; DNA Damage ; Genomic Instability ; Humans ; Mitochondrial Dynamics ; bcl-2-Associated X Protein/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; bcl-2-Associated X Protein ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2022.03.019
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Genome-wide association study of milk production traits in a crossbred dairy sheep population using three statistical models.

Li, H / Wu, X-L / Tait, R G / Bauck, S / Thomas, D L / Murphy, T W / Rosa, G J M

Animal genetics

2020 Volume 51, Issue 4, Page(s) 624–628

Abstract: Milk production is one of the most important characteristics of dairy sheep, and the identification of genes affecting milk production traits is critical to understanding the genetics and improve milk production in future generations. Three statistical ... ...

Abstract	Milk production is one of the most important characteristics of dairy sheep, and the identification of genes affecting milk production traits is critical to understanding the genetics and improve milk production in future generations. Three statistical techniques, namely GWAS, ridge-regression BLUP and BayesC
MeSH term(s)	Animals ; Breeding ; Female ; Genome-Wide Association Study/veterinary ; Milk/metabolism ; Models, Genetic ; Models, Statistical ; Sheep, Domestic/genetics ; Sheep, Domestic/metabolism
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article
ZDB-ID	632766-7
ISSN	1365-2052 ; 0268-9146 ; 0268-9154
ISSN (online)	1365-2052
ISSN	0268-9146 ; 0268-9154
DOI	10.1111/age.12956
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Article ; Online: Mechanisms of mitophagy: putting the powerhouse into the doghouse.

Riley, Joel S / Tait, Stephen W G

Biological chemistry

2016 Volume 397, Issue 7, Page(s) 617–635

Abstract: Since entering our cells in an endosymbiotic event one billion years ago, mitochondria have shaped roles for themselves in metabolism, inflammation, calcium storage, migration, and cell death. Given this critical role in cellular homeostasis it is ... ...

Abstract	Since entering our cells in an endosymbiotic event one billion years ago, mitochondria have shaped roles for themselves in metabolism, inflammation, calcium storage, migration, and cell death. Given this critical role in cellular homeostasis it is essential that they function correctly. Equally critical is the ability of a cell to remove damaged or superfluous mitochondria to avoid potential deleterious effects. In this review we will discuss the various mechanisms of mitochondrial clearance, with a particular focus on Parkin/PINK1-mediated mitophagy, discuss the impact of altered mitophagy in ageing and disease, and finally consider potential therapeutic benefits of targeting mitophagy.
MeSH term(s)	Animals ; Autophagy ; Disease ; Humans ; Mitochondria/metabolism ; Mitochondria/pathology ; Protein Kinases/metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2016-07-01
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1334659-3
ISSN	1437-4315 ; 1431-6730 ; 1432-0355
ISSN (online)	1437-4315
ISSN	1431-6730 ; 1432-0355
DOI	10.1515/hsz-2016-0137
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Article ; Online: Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.

Kwizera, Elyahb A / Ou, Wenquan / Lee, Sojeong / Stewart, Samantha / Shamul, James G / Xu, Jiangsheng / Tait, Nancy / Tkaczuk, Katherine H R / He, Xiaoming

ACS nano

2022 Volume 16, Issue 7, Page(s) 11374–11391

Abstract: The circulating tumor cells (CTCs, the root cause of cancer metastasis and poor cancer prognosis) are very difficult to culture for scale- ... ...

Abstract	The circulating tumor cells (CTCs, the root cause of cancer metastasis and poor cancer prognosis) are very difficult to culture for scale-up
MeSH term(s)	Humans ; Epithelial Cell Adhesion Molecule ; Titanium ; Gold ; Cell Line, Tumor ; Neoplastic Cells, Circulating/pathology ; Dimethylpolysiloxanes ; Glutathione ; Polyethylene Glycols
Chemical Substances	Epithelial Cell Adhesion Molecule ; Titanium (D1JT611TNE) ; Gold (7440-57-5) ; baysilon (63148-62-9) ; Dimethylpolysiloxanes ; Glutathione (GAN16C9B8O) ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.2c05195
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Article ; Online: Correction to Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.

Kwizera, Elyahb A / Ou, Wenquan / Lee, Sojeong / Stewart, Samantha / Shamul, James G / Xu, Jiangsheng / Tait, Nancy / Tkaczuk, Katherine H R / He, Xiaoming

ACS nano

2022 Volume 16, Issue 11, Page(s) 19606

Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Published Erratum
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.2c10382
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