miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging DOI Creative Commons
Katarzyna Goljanek‐Whysall, Ana Soriano‐Arroquia, Rachel McCormick

et al.

Aging Cell, Journal Year: 2020, Volume and Issue: 19(4)

Published: April 1, 2020

Abstract One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation dynamics essential to maintain a healthy population and prevent accumulation damaged mitochondria; however, regulatory are poorly understood. We demonstrated loss content in concomitant with dysregulation miR‐181a target interactions. Using approaches mito‐QC assay, we have established that an endogenous regulator through concerted regulation Park2, p62/SQSTM1, DJ‐1 vitro. Downregulation age was associated autophagy‐related proteins abnormal mitochondria. Restoring levels old mice prevented p62, DJ‐1, PARK2, improved quality function. These results provide physiological evidence for potential microRNA‐based interventions age‐related atrophy wider significance diseases

Language: Английский

Mitochondrial translation is required for sustained killing by cytotoxic T cells DOI
Miriam Lisci, P. Barton, Lyra O. Randzavola

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6565)

Published: Oct. 15, 2021

Mitochondria drive CTLs’ killer instinct Cytotoxic T lymphocytes (CTLs) can terminate both virally infected cells and cancer by secreting cytolytic proteins such as perforin granzyme B. CTLs are particularly effective because they sequentially kill multiple targets in a process called serial killing. Lisci et al . have identified mitochondria important regulators of CTL Mice lacking the deubiquitinase USP30 acutely depleted mitochondria, these reduced killing ability but normal motility, signaling, secretion. Surprisingly, mitochondria’s metabolic functions were not required for this process. Rather, mitochondrial translation proved indispensable protein synthesis sustained —STS

Language: Английский

Citations

89
Semi-automated quantitation of mitophagy in cells and tissues DOI Creative Commons
Lambert Montava‐Garriga, François Singh, Graeme Ball

et al.

Mechanisms of Ageing and Development, Journal Year: 2019, Volume and Issue: 185, P. 111196 - 111196

Published: Dec. 13, 2019

Mitophagy is a natural phenomenon and entails the lysosomal degradation of mitochondria by autophagy pathway. In recent years, development fluorescent pH-sensitive mitochondrial reporters has greatly facilitated monitoring mitophagy distinguishing between cytosolic or those delivered to acidic lysosomes. We recently published mito-QC reporter, which consists outer membrane-localised tandem mCherry-GFP tag. This allows quantification via increase in red-only mCherry signal that arises when GFP quenched upon delivery Here we develop macro for FIJI, Counter, describe its use allow reliable consistent semi-automated mitophagy. this methods article step-by-step how detect quantify show levels can be reliably calculated different cell lines under distinct stimuli. Finally, Counter used tissues transgenic mice. demonstrate skeletal muscle correlates with glycolytic activity. Our present data FIJI enables robust both vitro vivo.

Language: Английский

Citations

80
Mitophagy in the Pathogenesis of Liver Diseases DOI Creative Commons
Po‐Yuan Ke

Cells, Journal Year: 2020, Volume and Issue: 9(4), P. 831 - 831

Published: March 30, 2020

Autophagy is a catabolic process involving vacuolar sequestration of intracellular components and their targeting to lysosomes for degradation, thus supporting nutrient recycling energy regeneration. Accumulating evidence indicates that in addition being bulk, nonselective degradation mechanism, autophagy may selectively eliminate damaged mitochondria promote mitochondrial turnover, termed “mitophagy”. Mitophagy sequesters dysfunctional via ubiquitination cargo receptor recognition has emerged as an important event the regulation liver physiology. Recent studies have shown mitophagy participate pathogenesis various diseases, such injury, steatosis/fatty disease, hepatocellular carcinoma, viral hepatitis, hepatic fibrosis. This review summarizes current knowledge on molecular regulations functions physiology roles development liver-related diseases. Furthermore, therapeutic implications design new strategy cure diseases are discussed.

Language: Английский

Citations

79
Mitophagy and Innate Immunity in Infection. DOI
Dong‐Hyung Cho, Jin Kyung Kim, Eun‐Kyeong Jo

et al.

PubMed, Journal Year: 2020, Volume and Issue: 43(1), P. 10 - 22

Published: Jan. 31, 2020

Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial inducing clearance damaged mitochondria via autophagic machinery. Accumulating evidence suggests mitophagy modulated various microbial components in an attempt to affect innate immune response infection. In addition, plays a key role regulation inflammatory signaling, danger signals such as DNA translocated into cytosol can lead exaggerated responses. this review, we present current knowledge on functional aspects its crosstalk with signaling during A deeper understanding could facilitate development more effective therapeutic strategies against infections.

Language: Английский

Citations

73
Friendly mediates membrane depolarization-induced mitophagy in Arabidopsis DOI Creative Commons
Juncai Ma, Zizhen Liang, Jierui Zhao

et al.

Current Biology, Journal Year: 2021, Volume and Issue: 31(9), P. 1931 - 1944.e4

Published: March 12, 2021

Language: Английский

Citations

73
Fermented Soy Products: Beneficial Potential in Neurodegenerative Diseases DOI Creative Commons
Chan Ho Jang, Jisun Oh,

Ji Sun Lim

et al.

Foods, Journal Year: 2021, Volume and Issue: 10(3), P. 636 - 636

Published: March 18, 2021

Fermented soybean products, such as cheonggukjang (Japanese natto), doenjang (soy paste), ganjang sauce), and douchi, are widely consumed in East Asian countries major sources of bioactive compounds. The fermentation cooked with bacteria (Bacillus spp.) fungi (Aspergillus spp. Rhizopus produces a variety novel compounds, most which possess health benefits. This review is focused on the preventive ameliorative potential fermented soy foods their components to manage neurodegenerative diseases, including Alzheimer’s Parkinson’s diseases.

Language: Английский

Citations

72
BNIP3L/NIX regulates both mitophagy and pexophagy DOI Creative Commons
Léa P. Wilhelm, Juan Zapata‐Muñoz, Beatriz Villarejo‐Zori

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(24)

Published: Oct. 10, 2022

Abstract Mitochondria and peroxisomes are closely related metabolic organelles, both in terms of origin function. can also be turned over by autophagy, processes termed mitophagy pexophagy, respectively. However, despite their close relationship, it is not known if organelles under similar conditions, so, how this might coordinated molecularly. Here, we find that multiple selective autophagy pathways activated upon iron chelation show pexophagy occur a BNIP3L/NIX‐dependent manner. We reveal the outer mitochondrial membrane‐anchored NIX protein, previously described as receptor, independently localises to drives pexophagy. process happens vivo , with mouse tissue lacks having higher peroxisomal content. further stimulated same physiological conditions activate mitophagy, including cardiomyocyte erythrocyte differentiation. Taken together, our work uncovers dual role for NIX, only but thus illustrating interconnection between pathways.

Language: Английский

Citations

66
Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification? DOI Creative Commons
Kanchan Phadwal, Christina Vrahnas, Ian G. Ganley

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 16, 2021

Mitochondria are crucial bioenergetics powerhouses and biosynthetic hubs within cells, which can generate sequester toxic reactive oxygen species (ROS) in response to oxidative stress. Oxidative stress-stimulated ROS production results ATP depletion the opening of mitochondrial permeability transition pores, leading mitochondria dysfunction cellular apoptosis. Mitochondrial loss function is also a key driver acquisition senescence-associated secretory phenotype that drives senescent cells into pro-inflammatory state. Maintaining homeostasis for retaining contractile vascular smooth muscle (VSMCs), most prominent vasculature. Loss this associated with metabolic shift glycolysis. Emerging evidence suggests may play direct role calcification underlying pathologies including (1) impairment by mineral dysregulation i.e., calcium phosphate overload patients end-stage renal disease (2) presence increased calcific aortic valve disease, atherosclerosis, type-II diabetes chronic kidney disease. In review, we discuss cause consequence pathologies; autophagy mitophagy pathways preventing during finally ROS, DRP1, HIF-1 as potential novel markers therapeutic targets maintaining calcification.

Language: Английский

Citations

61
Mosaic dysfunction of mitophagy in mitochondrial muscle disease DOI Creative Commons
Takayuki Mito, Amy E. Vincent, Julie Faitg

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(2), P. 197 - 208.e5

Published: Jan. 13, 2022

Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report mitophagy contributes to mitochondrial dysfunction skeletal muscle of aged mice human patients. The early disease stage characterized by fibers with central nuclei, enhanced around these nuclei. However, progressive halts disrupts lysosomal homeostasis. Interestingly, activated or halted occur mosaic manner even adjacent fibers, indicating cell-autonomous regulation. Rapamycin restores turnover, mTOR-dependence recycling advanced stage. Our evidence suggests (1) hallmark age-related pathology muscle, (2) halting explaining respiratory chain deficiency accumulation pathogenic mtDNA variants adult-onset diseases normal aging, (3) augmenting promising therapeutic approach for dysfunction.

Language: Английский

Citations

60
GAK and PRKCD are positive regulators of PRKN-independent mitophagy DOI Creative Commons
Michael J. Munson, Benan John Mathai, Matthew Yoke Wui Ng

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 20, 2021

The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators PRKN-independent using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as mitophagy, with both being dispensable PRKN-dependent starvation-induced autophagy. demonstrate that the activity GAK PRKCD are required efficient vitro, is present on mitochondria, facilitates recruitment ULK1/ATG13 to early autophagic structures. Importantly, vivo relevance kinases regulation basal mitophagy. Knockdown homologue (gakh-1) C. elegans knockout homologues zebrafish led significant inhibition highlighting evolutionary these regulation.

Language: Английский

Citations

59