Implications of Altered Endosome and Lysosome Biology in Space Environments
Abstract
:1. Introduction
2. The Endosome-Lysosome System and Autophagy in Microgravity-Induced Pathophysiology
2.1. Bone Loss
2.2. Muscle Atrophy
2.3. Cell Differentiations
2.4. Oxidative Metabolism
2.5. The Lysosomal System as a Monitor for Physiological Stress
3. Discussion and Conclusion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
µg | Microgravity |
ROS | Reactive oxygen species |
TFEB | Transcription factor EB |
RPM | Random positioning machine |
RWV | Rotating wall vessel |
SR | Sarcoplasmic reticulum |
EEA1 | Early Endosome Antigen 1 |
M6PR | Mannose-6-phosphate receptor |
TRPML1 | Transient receptor potential cation channel 1 |
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Physiological, Protein, Gene or Organelle Change | Effect | Organism/Model System | Radiation or Simulated/Real µg | Ref. |
---|---|---|---|---|
Lysosomes, phagosomes | Increased | Purkinje cells, Rat | Radiation (291 Mev/nucleon, 100–300/mm2) | [26] |
Autophagosomes | Increased | Myocardia, Rat | Microgravity (Real) | [22] |
Lysosomal activity | Elevated | Bone | Microgravity (Real) | [27] |
Autophagic vacuoles, endocytic vesicles, lysosomes | Increased number, size | Salivary gland, Rat & Mouse | Microgravity (Real) | [23,28] |
Lysosomal tripeptidyl peptidase | Altered distribution | Skeletal muscle, Rat | Microgravity (Real) | [29] |
Sarcoplasmic reticulum (SR) | Localise to myofibril disruptions – may release Ca2+, may induce autophagy | |||
Glutathione | Decreased | Liver, mouse | Microgravity (Real) | [19] |
Lipid membrane metabolism, endocytosis, inflammatory pathways | Enriched | |||
MuRF-1, MAFbx | Increased expression | Soleus and EDL muscle, mice | Microgravity (Real) | [30] |
LC3β, CTSL | Unchanged | |||
IGF-1 and IL-6 | Increased in EDL, Decreased in Soleus | |||
c-Fos | Upregulated | Supraoptic neurons, Rat | Microgravity (Real) | [31] |
Vasopressin | Downregulated | |||
Autophagosomes, lysosome-like bodies | Increased | Osteocytes and Soleus myotendinous junction, Rhesus monkey | Microgravity (Real) | [32,33] |
Lactate dehydrogenase type A | Mono-ubiquitinated | Myoblastic L6 cells, Rat | Microgravity (Simulated, tail suspension) | [34] |
Ubiquitinated protein & MAFbx, Murf-1, Nedd4, XIAP | Upregulated expression | Soleus Muscle, Rat | Microgravity (Simulated, hindlimb suspension) | [35,36,37] |
Glucose metabolism | Increased response upon muscle atrophy | |||
Proteolysis | Increased (Ca2+ regulated from SR?) | |||
Lysosomal and Ca2+-dependent proteolysis | Enhanced activity | |||
Cathepsin B, D, L | Upregulated expression | |||
N-acetylglucosaminidase (lysosomal) | Increased activity | Gastrocnemius & soleus muscle, CD1 mice | Microgravity (Simulated, hindlimb suspension) | [38,39] |
Bcl-2, Bax | Increased expression ratio | |||
Vps34, Beclin-1, Cathepsin D | Upregulated | Cardiac tissue, rat | Microgravity (Simulated, tail suspension) | [40] |
p62 | Downregulated | |||
mTOR | Decreased phosphorylation (s2448) | |||
Ca2+ | Oscillates | HEK293, Myoblast C2C12, Mouse bone marrow, RAW 264.7 osteoclast progenitor, MC3T3-E1, HepG2, colorectal, HUVEC, L-540, HDLM-2 cell lines | Microgravity (Simulated, clinostat & RWV) | [4,5,41,42,43,44,45,46,47] |
LC3 +ve autophagosomes | Increased puncta (72 h) | |||
LC3-II | Increased conversion from LC3-I | |||
AMPK, T172, ULK1, ATF4, Beclin-1 | Increased phosphorylation | |||
AMPK S485 | Reduced phosphorylation at 24 h only | |||
ATG12, ATG5, ATP1A1, ATP5A1, Bcl-2, MnSOD, Cu/ZnSOD, Mcl-1, mTOR, Rab7, GPCR, P58 | Downregulated | |||
ATG14, ATG16L1, ATG4B, ATG7, ATG5, Bax, Beclin-1, Ire1α, LC3, MnSOD, p62, Syncytin-A Tnfsf10, ULK1, MITF, s100a8, CREB, CXCL4 | Upregulated | |||
P62 | Reduced at 72h | |||
ROS | Elevated | |||
Cytoskeleton | Temporary collapse of microvilli at 24 h & altered microtubule/actin remodelling | TCam-2 seminoma cell line | Microgravity (Simulated, RPM) | [48,49] |
LC3 +ve autophagosomes | Increased | |||
LC3-II | Increased conversion from LC3-I | |||
Ca2+, ROS | Elevated temporarily at 24 h | |||
MnSOD, Casp9, BECN1 | Downregulated | NB-1 neuroblastoma cell line | X-ray, Microgravity (Simulated, clinostat) | [50] |
VDAC2 | Upregulated | |||
Vps15, Atg14L, Beclin1, p62, FOXO3A | Downregulated | Endometrial stromal cells | Microgravity (Simulated, RPM) | [51] |
LC3BII | Decreased |
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Johnson, I.R.D.; Nguyen, C.T.; Wise, P.; Grimm, D. Implications of Altered Endosome and Lysosome Biology in Space Environments. Int. J. Mol. Sci. 2020, 21, 8205. https://doi.org/10.3390/ijms21218205
Johnson IRD, Nguyen CT, Wise P, Grimm D. Implications of Altered Endosome and Lysosome Biology in Space Environments. International Journal of Molecular Sciences. 2020; 21(21):8205. https://doi.org/10.3390/ijms21218205
Chicago/Turabian StyleJohnson, Ian R. D., Catherine T. Nguyen, Petra Wise, and Daniela Grimm. 2020. "Implications of Altered Endosome and Lysosome Biology in Space Environments" International Journal of Molecular Sciences 21, no. 21: 8205. https://doi.org/10.3390/ijms21218205