Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Autophagy, Год журнала: 2016, Номер 12(1), С. 1 - 222

Опубликована: Янв. 2, 2016

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially multicellular eukaryotes. For example, a key point needs emphasized difference between measurements monitor numbers or volume autophagic elements (e.g., autophagosomes autolysosomes) at any stage process versus those flux through pathway (i.e., complete including amount rate cargo sequestered degraded). particular, block macroautophagy results autophagosome accumulation must differentiated from stimuli increase activity, defined as increased induction coupled with delivery to, degradation within, lysosomes (in most higher eukaryotes some protists such Dictyostelium) vacuole plants fungi). other words, investigators field understand appearance more does not necessarily equate fact, cases, accumulate because trafficking without concomitant change biogenesis, whereas an autolysosomes may reflect reduction degradative activity. It worth emphasizing here lysosomal digestion evaluating its competence crucial part evaluation flux, autophagy. Here, present selection interpretation use by who aim examine related processes, well reviewers need provide realistic reasonable critiques papers are focused processes. These meant formulaic rules, appropriate depend question being asked system used. addition, emphasize no individual assay guaranteed one every situation, strongly recommend multiple Along lines, potential pleiotropic effects due blocking genetic manipulation, imperative target gene knockout RNA interference than autophagy-related protein. Atg proteins, groups involved cellular pathways implying all proteins can specific marker process. guidelines, consider various assessing what information can, cannot, obtained them. Finally, discussing merits limits particular assays, hope encourage technical innovation

Язык: Английский

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Parkinson disease

Nature Reviews Disease Primers, Год журнала: 2017, Номер 3(1)

Опубликована: Март 22, 2017

Язык: Английский

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Ageing as a risk factor for neurodegenerative disease

Nature Reviews Neurology, Год журнала: 2019, Номер 15(10), С. 565 - 581

Опубликована: Сен. 9, 2019

Язык: Английский

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The PI3K Pathway in Human Disease

Cell, Год журнала: 2017, Номер 170(4), С. 605 - 635

Опубликована: Авг. 1, 2017

Язык: Английский

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹

Autophagy, Год журнала: 2021, Номер 17(1), С. 1 - 382

Опубликована: Янв. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Язык: Английский

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Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

Molecules, Год журнала: 2019, Номер 24(8), С. 1583 - 1583

Опубликована: Апрель 22, 2019

Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes reduction antioxidants, which turn produce an oxidation–reduction imbalance organisms. Paucity the antioxidant system generates oxidative-stress, characterized by elevated levels reactive species (oxygen, hydroxyl free radical, so on). Mitochondria play key role ATP supply to cells via oxidative phosphorylation, well synthesis essential biological molecules. Various redox reactions catalyzed enzymes take place phosphorylation process. An inefficient may generate oxygen (ROS), leading mitochondrial dysfunction. Mitochondrial metabolism, phospholipid proteolytic pathways are found be major potential source radicals. A lower concentration ROS for normal cellular signaling, whereas higher long-time exposure cause damage macromolecules such DNA, lipids proteins, ultimately resulting necrosis apoptotic cell death. Normal proper functioning central nervous (CNS) entirely dependent on chemical integrity brain. It established that brain consumes large amount highly rich lipid content, becoming prone stress. high consumption leads excessive production ROS. Apart from this, neuronal membranes polyunsaturated fatty acids, susceptible neurodegenerative diseases Parkinson’s disease (PD), Alzheimer’s (AD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), among others, can result biochemical alteration (due stress) bimolecular components. There need understand processes diseases. This review effort towards improving our understanding pivotal played OS

Язык: Английский

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Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance

Current Biology, Год журнала: 2018, Номер 28(4), С. R170 - R185

Опубликована: Фев. 1, 2018

Язык: Английский

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The Mitochondrial Basis of Aging

Molecular Cell, Год журнала: 2016, Номер 61(5), С. 654 - 666

Опубликована: Март 1, 2016

A decline in mitochondrial quality and activity has been associated with normal aging correlated the development of a wide range age-related diseases. Here, we review evidence that mitochondria function contributes to aging. In particular, discuss how contribute specific aspects process, including cellular senescence, chronic inflammation, age-dependent stem cell activity. Signaling pathways regulating unfolded protein response mitophagy are also reviewed, particular emphasis placed on these might, turn, regulate longevity. Taken together, observations suggest influence or number key strategies directed at improving might have far-reaching beneficial effects.

Язык: Английский

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Parkin and PINK1 mitigate STING-induced inflammation

Nature, Год журнала: 2018, Номер 561(7722), С. 258 - 262

Опубликована: Авг. 21, 2018

Язык: Английский

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NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria

Cell, Год журнала: 2016, Номер 164(5), С. 896 - 910

Опубликована: Фев. 1, 2016

Язык: Английский

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