Autophagy is required for spermatogonial differentiation in the Drosophila testis

Varga, Virginia B.; Schuller, Dóra; Szikszai, Fanni; Szinyákovics, Janka; Puska, Gina; Vellai, Tibor; Kovács, Tibor

doi:10.1007/s42977-022-00122-7

“…BMPs (Dpp and Gbb) are produced by both hub cells and CySCs, and upon binding, BMP receptors in GSCs suppress bag-of-marbles (bam), which promotes the differentiation program [153][154][155]. Dpp and Gbb from hub cells and CySCs activate BMP signaling in GSCs and non-autonomously suppress autophagy, which can be detected only at low/basal levels in the GSCs, as seen by reduced Atg5 and Atg8a expression [156]. Autophagy is upregulated, as seen by increased Atg5 expression and increased mCherryAtg8a puncta formation in the differentiated cells where BMP signaling is inactive and Bam is expressed.…”

Section: Cell Non-autonomous Autophagy In Ecm-mediated Regulation And...mentioning

confidence: 99%

“…However, the suppression of Atg8a by BMPs is not at the transcriptional level. Thus, BMPs signaling suppress autophagy in male GSCs cell non-autonomously and via distinct mechanisms [156].…”

Section: Cell Non-autonomous Autophagy In Ecm-mediated Regulation And...mentioning

confidence: 99%

Illuminating Intercellular Autophagy: A Comprehensive Review of Cell Non-Autonomous Autophagy

Selarka,

Shravage

2024

Preprint

0

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Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

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“…BMPs (Dpp and Gbb) are produced by both hub cells and CySCs, and upon binding, BMP receptors in GSCs suppress bag-ofmarbles (bam), which promotes the differentiation program [152][153][154]. Dpp and Gbb from hub cells and CySCs activate BMP signaling in GSCs and non-autonomously suppress autophagy, which can be detected only at low/basal levels in the GSCs, as seen by reduced Atg5 and Atg8a expression [155]. Autophagy is upregulated, as seen by increased Atg5 expression and increased mCherryAtg8a puncta formation in the differentiated cells where BMP signaling is inactive and Bam is expressed.…”

Section: Cell Non-autonomous Autophagy In Ecm-mediated Regulation And...mentioning

confidence: 99%

“…However, the suppression of Atg8a by BMPs is not at the transcriptional level. Thus, BMPs signaling suppress autophagy in male GSCs cell non-autonomously and via distinct mechanisms [155].…”

Section: Cell Non-autonomous Autophagy In Ecm-mediated Regulation And...mentioning

confidence: 99%

Illuminating Intercellular Autophagy: A Comprehensive Review of Cell Non-Autonomous Autophagy

Selarka,

Shravage

2024

Preprint

0

View full text Add to dashboard Cite

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

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“…Ultrastructural analysis of the IFM samples was performed according to [66,67]. Durcupan/Fluca was used for embedding (Sigma-Aldrich, 44610-1EA).…”

Section: Electron Microscopymentioning

confidence: 99%

The Small-Molecule Enhancers of Autophagy AUTEN-67 and -99 Delay Ageing in Drosophila Striated Muscle Cells

Komlós

¹

,

Szinyákovics

²

,

Falcsik

³

et al. 2023

IJMS

Self Cite

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Background: Autophagy (cellular self-degradation) plays a major role in maintaining the functional integrity (homeostasis) of essentially all eukaryotic cells. During the process, superfluous and damaged cellular constituents are delivered into the lysosomal compartment for enzymatic degradation. In humans, age-related defects in autophagy have been linked to the incidence of various age-associated degenerative pathologies (e.g., cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency) and accelerated ageing. Muscle mass decreases at detectable levels already in middle-aged patients, and this change can increase up to 30–50% at age 80. AUTEN-67 and -99, two small-molecule enhancers of autophagy with cytoprotective and anti-ageing effects have been previously identified and initially characterized. These compounds can increase the life span in wild-type and neurodegenerative model strains of the fruit fly Drosophila melanogaster. Methods: Adult flies were treated with these AUTEN molecules via feeding. Fluorescence and electron microscopy and Western blotting were used to assess the level of autophagy and cellular senescence. Flying tests were used to measure the locomotor ability of the treated animals at different ages. Results: In the current study, the effects of AUTEN-67 and -99 were observed on striated muscle cells using the Drosophila indirect flight muscle (IFM) as a model. The two molecules were capable of inducing autophagy in IFM cells, thereby lowering the accumulation of protein aggregates and damaged mitochondria, both characterizing muscle ageing. Furthermore, the two molecules significantly improved the flying ability of treated animals. Conclusions: AUTEN-67 and -99 decrease the rate at which striated muscle cells age. These results may have a significant medical relevance that could be further examined in mammalian models.

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Autophagy is required for spermatogonial differentiation in the Drosophila testis

Cited by 8 publications

References 68 publications

Illuminating Intercellular Autophagy: A Comprehensive Review of Cell Non-Autonomous Autophagy

Illuminating Intercellular Autophagy: A Comprehensive Review of Cell Non-Autonomous Autophagy

Illuminating Intercellular Autophagy: A Comprehensive Review of Cell Non-Autonomous Autophagy

The Small-Molecule Enhancers of Autophagy AUTEN-67 and -99 Delay Ageing in Drosophila Striated Muscle Cells

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