# Metabolic Regulation in the Maintenance of Drosophila Testis Stem Cells

**Authors:** Jiao Liu, Peixin Xu, Yichen Liu, Yuke Xie, Zixuan Liu, Gyeong Hun Baeg

PMC · DOI: 10.3390/ijms27041884 · International Journal of Molecular Sciences · 2026-02-15

## TL;DR

This review explores how metabolism regulates stem cell maintenance in fruit fly testes, with implications for understanding human stem cells and aging.

## Contribution

The paper synthesizes current knowledge on metabolic regulation of Drosophila testis stem cells and identifies future research directions.

## Key findings

- Germline and somatic stem cells in Drosophila testes have distinct metabolic profiles linked to mitochondrial dynamics and redox homeostasis.
- Metabolic intermediates act as signaling molecules, influencing niche-stem cell interactions and epigenetic modifications.
- Dysregulation of metabolic homeostasis leads to stem cell depletion and reproductive decline in aging.

## Abstract

Stem cells maintain tissue homeostasis through precisely regulated self-renewal and differentiation, processes largely dependent on metabolic control. The Drosophila testis provides an ideal model system to study metabolism regulation of stem cell homeostasis due to many advantages, including its well-defined stem cell niche architecture and genetic tractability. Recent studies have revealed that germline stem cells (GSCs) and somatic cyst stem cells (CySCs) exhibit distinct metabolic profiles. In particular, GSCs exhibit a metabolic feature closely associated with mitochondrial dynamics, lipid metabolism, and redox homeostasis, all of which are essential for maintaining their stem identity through the regulation of TOR (Target of Rapamycin) signaling. Nutrient sensing through the insulin/TOR, BMP, and JAK-STAT pathways integrates nutritional cues with developmental programs. Lipid metabolism and membrane homeostasis further contribute to the maintenance of stem cells. Metabolic intermediates function as signaling molecules, modulating niche-stem cell interactions and epigenetic modifications in stem cells. Hence, dysregulation of metabolic homeostasis can lead to stem cell depletion and age-related reproductive decline. This review synthesizes the current understanding of metabolic regulation in Drosophila testis stem cell maintenance, identifies critical knowledge gaps, and explores future research directions such as spatial/temporal metabolomics approaches. Lastly, we highlight how these insights may help understand mammalian stem cell biology and regenerative medicine.

## Linked entities

- **Genes:** RORC (RAR related orphan receptor C) [NCBI Gene 6097], PIN (insulin precursor) [NCBI Gene 100533403], dpp (decapentaplegic) [NCBI Gene 33432]
- **Species:** Drosophila (taxon 7215)

## Full-text entities

- **Genes:** Pdha (Pyruvate dehydrogenase E1 alpha subunit) [NCBI Gene 31406] {aka CG 7010, CG7010, Dmel\CG7010, E1-PDH, L(1)G0334, L(1)g0334}, Ilp5 (Insulin-like peptide 5) [NCBI Gene 2768992] {aka CG33273, DILP, DILP 5, DILP-5, DILP5, DILPs}, Glut1 (Glucose transporter 1) [NCBI Gene 38109] {aka 0074/12, CG1086, CG13908, CG43946, DmGLUT1, DmGluT1}, AMPKalpha (AMP-activated protein kinase alpha subunit) [NCBI Gene 43904] {aka AK, AMPK, AMPK alpha, AMPK-alpha, Ampk, CG3051}, N (Notch) [NCBI Gene 31293] {aka 1.1, 16-178, 16-55, Ax, CG3936, CT13012}, mTor (mechanistic Target of rapamycin) [NCBI Gene 47396] {aka 5092, CG5092, CT16317, CT24745, CT24817, DmTOR}, upd1 (unpaired 1) [NCBI Gene 32813] {aka CG5993, Dmel\CG5993, OS, Os, UPD, Unpaireds}, esg (escargot) [NCBI Gene 34903] {aka 4B7, BG01042, BG:DS07851.7, CG3758, Dmel\CG3758, br43}, Myc (Myc) [NCBI Gene 31310] {aka CG10798, D-Myc, DM, DMYc, Diminutive, Dm}, upd3 (unpaired 3) [NCBI Gene 3346149] {aka CG15062, CG15062/CG5963, CG33542, CG5963, Dmel\CG33542, Unpaireds}, Act79B (Actin 79B) [NCBI Gene 40444] {aka 143060_f_at, ACT4, Actin, ArpF, CG7478, D}, raptor (raptor) [NCBI Gene 31543] {aka 4320, CG4320, Dmel\CG4320, dRAPTOR, dRap, dRaptor}, Atg8a (Autophagy-related 8a) [NCBI Gene 32001] {aka ATG8, ATG8/LC3, Atg-8a, Atg8, Atg8/LC3, Atg8alpha}, Irp-1A (Iron regulatory protein 1A) [NCBI Gene 42689] {aka C-Acon, CG4900, Dmel\CG4900, IRF, IRP, IRP-1}, Marf (Mitochondrial assembly regulatory factor) [NCBI Gene 31581] {aka CG3869, CG38869, Dmel\CG3869, MFN, MFN2, Marf-1}, Opa1 (Optic atrophy 1) [NCBI Gene 36578] {aka CG8479, Dmel\CG8479, OPA1-like, Opa1-like, dOPA1, dOpa}, S6k (Ribosomal protein S6 kinase) [NCBI Gene 38654] {aka 10539, 7-10, 7084, CG10539, DS6K, Dmel\CG10539}, SdhC (Succinate dehydrogenase, subunit C) [NCBI Gene 41340] {aka BcDNA:RH04289, C560, CG6666, Dmel\CG6666, RH04289p, SDH}, Inx2 (Innexin 2) [NCBI Gene 31646] {aka CG4590, D-inx-2, Dm-Inx2, Dm-inx, Dm-inx2, Dmel\CG4590}, Pdh (Photoreceptor dehydrogenase) [NCBI Gene 39812] {aka CG4899, Dmel\CG4899, pcdr}, dpp (decapentaplegic) [NCBI Gene 33432] {aka BMP, Bmp, CG9885, DPP-C, Dm-DPP, DmDPP}, foxo (forkhead box, sub-group O) [NCBI Gene 41709] {aka 3143, Afx, Akh, CG3143, DFOXO, DfoxO}, bam (bag of marbles) [NCBI Gene 43038] {aka Bam-C, BamC, BamF, CG10422, Dmel\CG10422, alpha}, Mgtor (Megator) [NCBI Gene 36264] {aka Bx34, CG8274, Dmel\CG8274, MTOR, Mtor, TPR}, Vhl (von Hippel-Lindau) [NCBI Gene 53433] {aka BcDNA:RH61560, CG13221, DVhl, Dmel\CG13221, Dvhl, d-VHL}, p38b (p38b MAP kinase) [NCBI Gene 34780] {aka 186F5S, BG:DS00797.3, CG7393, D-p38, D-p38 MAPK, D-p38b}, cnc (cap-n-collar) [NCBI Gene 42743] {aka 5134, BcDNA:RE05559, CG13826, CG17894, CG43286, CG4566}, hop (hopscotch) [NCBI Gene 32080] {aka 4, CG1594, Dm JAK, DmHD-160, Dmel\CG1594, HD-160}, zpg (zero population growth) [NCBI Gene 251414] {aka CG10125, Dm-inx4, Dmel\CG10125, FBpp0076692, Inx4, innexin4}, gbb (glass bottom boat) [NCBI Gene 37778] {aka 60A, BMP, CG5562, Dm-GBB, DmGBB, Dmel\CG5562}, Thor (thor) [NCBI Gene 33569] {aka 153432_at, 43-BP, 4E-BP, 4E-BP1, 4EBP, 4e-BP}, sima (similar) [NCBI Gene 43580] {aka 7951, CG31031, CG45051, CG7951, DMU43090, Dmel\CG45051}, Pdk (Pyruvate dehydrogenase kinase) [NCBI Gene 35970] {aka BcDNA:LD09837, CG8808, DmPDK, DmPdk, Dmel\CG8808, PDHK}, Mad (Mothers against dpp) [NCBI Gene 33529] {aka 2/23, CG12399, Dmel\CG12399, E(zen)2, En(vvl), Mat}, Ldh (Lactate dehydrogenase) [NCBI Gene 45880] {aka CG10160, Dmel\CG10160, IMP-L3, IMPL3, Imp-L3, ImpL3}, Pdp (Pyruvate dehydrogenase phosphatase) [NCBI Gene 31683] {aka 153332_at, CG12151, Dmel\CG12151}, Akt (Akt kinase) [NCBI Gene 41957] {aka AKT-1, AKT/PKB, AKT1, Akt-1, Akt/PKB, Akt1}, spi (spitz) [NCBI Gene 35253] {aka CG10334, CT29014, Dmel\CG10334, EP(2)2378, Spitz, anon-WO0118547.158}, chico (chico) [NCBI Gene 64880] {aka BcDNA.GH11263, BcDNA:GH11263, CG5686, Chico/IRS, Dmel\CG5686, IRS}, Ald1 (Aldolase 1) [NCBI Gene 43183] {aka ALD, ALDOA, Ald, Aldolase, BcDNA:LP07735, CG6058}, Atg1 (Autophagy-related 1) [NCBI Gene 39454] {aka CG10967, DK-4, DmATG1, Dmel\CG10967, ULK1, UNC 51-like}, Drp1 (Dynamin related protein 1) [NCBI Gene 33445] {aka CG3210, DNM1L, DRP, Dmel\CG3210, Dnm1/Drp1, Drp}, Egfr (Epidermal growth factor receptor) [NCBI Gene 37455] {aka C-erb, CG10079, D-EGFR, D-Egf, DEGFR, DER}, Keap1 (Keap1) [NCBI Gene 42062] {aka CG3962, DmKeap1, Dmel\CG3962, Keap-1, Nrf-2, dKEAP1}, Stat92E (Signal-transducer and activator of transcription protein at 92E) [NCBI Gene 42428] {aka CG4257, D-STAT, D-Stat, D-stat, D-stat/stat92E, DRODSRC}, SREBP (Sterol regulatory element binding protein) [NCBI Gene 40155] {aka CG8522, Dmel\CG8522, HLH106, HlH106, SREBF1, SREBP1}, Pi3K21B (Pi3K21B) [NCBI Gene 33203] {aka CG2699, Dmel\CG2699, Dp60, P60, PI(3)K, PI3 kinase}, tgo (tango) [NCBI Gene 41084] {aka ARNT, Arnt, CG11987, DARNT, Dmel\CG11987, HIF-1}, InR (Insulin-like receptor) [NCBI Gene 42549] {aka 18402, CG18402, DIHR, DILR, DIR, DIRH}
- **Diseases:** muscle dysfunction (MESH:D009135), parasitic infection (MESH:D010272), hypoxic (MESH:D002534), GSCs (MESH:D000092423), hypoxia (MESH:D000860), cyst (MESH:D003560), metabolic dysfunction (MESH:D008659), mitochondrial dysfunction (MESH:D028361), inflammatory (MESH:D007249), injury to (MESH:D014947), hyperglycemia (MESH:D006943), insulin resistance (MESH:D007333), infection (MESH:D007239), cancer (MESH:D009369)
- **Chemicals:** glycogen (MESH:D006003), nucleotide (MESH:D009711), Lipid (MESH:D008055), ATP (MESH:D000255), leucine (MESH:D007930), ROS (MESH:D017382), blood sugar (MESH:D001786), acid (MESH:D000143), Oxygen (MESH:D010100), pyruvate (MESH:D019289), Glass bottom boat (-), triglycerides (MESH:D014280), fatty acid (MESH:D005227), carbohydrate (MESH:D002241), TCA (MESH:D014233), lactate (MESH:D019344), amino acid (MESH:D000596)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** Hub — Canis lupus familiaris (Dog), Canine mammary carcinoma, Cancer cell line (CVCL_C1IJ), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

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## References

78 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941318/full.md

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Source: https://tomesphere.com/paper/PMC12941318