discuss the clinical implications of this branch of membrane biology. Did the article mention specific diseases related to this field? Search for other articles in this field and mention your findings in your thread.

Min of 500 word.

Then i need you to reply to these two post regarding the article (250 word min)

For your replies, based on the course material, speculate how dietary intake of specific lipids would affect or create disorders in the area of membrane biology that at least 2 of your classmates have mentioned. You may be imaginative as long as the biology is reasonable.

first post

In this review article Membrane-bending proteins, the researchers focused on the protein directly bend the membranes and how they promote curvature. The membrane shapes include flat and fenestrated sheets, vesicles, tubules, cisternae, and vesicles. The shape of the membrane is determined by the complex interactions of lipids and proteins. There are three mechanisms used to understand membrane-deforming. The first mechanism is membranes can be pulled, pushed, or held in shape by interactions with the cytoskeleton, particularly actin filaments and microtubules. The second mechanism is, membrane morphology and dynamics can also be affected by the heterogeneous distribution of some lipids within a bilayer. The third mechanism is a growing number of proteins have been shown to directly bend membranes (Prinz & Hinshaw, 2009). Since the review article focuses on the proteins that directly bend and form the curve, the researchers have to analyze the three mechanisms used to generate membrane curvature and oligomerize to stabilize it. The first mechanism is that some proteins bend membranes by inserting amphipathic domains partially into the bilayer. The second mechanism of membrane bending is the formation of a rigid scaffold that deforms the underlying membrane or stabilizes membranes that have been bent by other mechanisms. The third mechanism has evidence that certain some proteins deform membranes by causing lipid clustering (Prinz & Hinshaw, 2009).

The article did not mention specific diseases related to membrane-bending. It is minimal research about membrane-bending proteins and the types of human diseases that are caused by membrane-bending. In Membrane-bending, Prinz & Hinshaw mentioned several of proteins that are involved with membrane-bending and the significance of their function in membrane-bending. Caveolins could also bend the caveolae membranes by altering the clustering or ordering of lipids (Prinz & Hinshaw, 2009). If there is alteration in the ordering of lipids. It can cause lipid diseases such as, lysosomal storage disorder. Lysosomal storage disorder is caused by major changes in certain components of its’ order phase. Cystic fibrosis (CF) is a disease caused by misfolded proteins The misfolded proteins encoded by mutant genes and ER stress causes this disease.

The physiological implications of this crowded environment are just beginning to be explored. The density-dependent tubulation by ENTH domains, ANTH domains and membrane-bound GFP suggests a general mechanism by which steric congestion on cellular membranes could assist in curvature generation (Stachowiak, Schmid, Ryan, et.al, 2012). The protein crowding at the membrane surface drives bending away from the adhered proteins, the balance between lateral pressures on each surface of the membrane could determine its shape, such that regions curved in either direction could arise from local asymmetries in protein density (Stachowiak, Schmid, Ryan, et.al, 2012). Further research studies need to be conducted to fully understand the mechanisms membrane-bending proteins. Further research will allow researchers to find diseases and diagnosis related to membrane-bending.

References:

1. Ferreira, C. R., & Gahl, W. A. (2017). Lysosomal storage diseases. Translational science of rare diseases, 2(1-2), 1–71. https://doi.org/10.3233/TRD-160005
2. Prinz, W. A., & Hinshaw, J. E. (2009). Membrane-bending proteins. Critical reviews in biochemistry and molecular biology, 44(5), 278–291. https://doi.org/10.1080/10409230903183472
3. Stachowiak, J. C., Schmid, E. M., Ryan, C. J., Ann, H. S., Sasaki, D. Y., Sherman, M. B., Geissler, P. L., Fletcher, D. A., & Hayden, C. C. (2012). Membrane bending by protein-protein crowding. Nature cell biology, 14(9), 944–949. https://doi.org/10.1038/ncb256

Second post:

The article Membrane-bending proteins, analyzes the influence proteins have in cellular/organelle membrane-bending. The research identified many mechanisms that can alter membrane shapes. Membrane-bending can occur due to interactions with the cytoskeleton or protein-lipid interactions. The researchers focused on examining how protein and lipid interactions alter the membrane shape. They determined that there are three mechanisms proteins use to bend the membrane shape. The first mechanism used by proteins is to insert amphipathic proteins (usually peripheral proteins) into one of the layers (leaflets) of the lipid bilayer, causing membrane folding. The second method can either deform the inner leaflet or stabilize an already bent segment caused by protein scaffolding (binding together multiple proteins). The final mechanism proteins use are alterations of lipid organization, which causes them to cluster together. The research conducted lists the different protein types involved in membrane bending: virus proteins, regulatory proteins, vesicular trafficking proteins, and domain proteins. The effects proteins have on organelle health were reviewed and documented (Prinz & Hinshaw, 2009).

The clinical implications of protein significance in membrane-bending is that future research can determine the repercussions of excessive membrane-bending. Future research can increase the understanding of the impact membrane-bending has on the organelle, cell, and individual. Understanding the mechanism of action that causes membrane deformation can lead to potential treatments for unnecessary membrane-bending. The article states that future research conducted should identify other proteins and protein-mechanisms involved in membrane-folding (Prinz & Hinshaw, 2009). Analysis of the health repercussions of altered membranes can also lead to the potential origin of different health care problems associated with problematic membrane-bending. Current research identifies membrane-bending, curvatures, and structure as crucial to the functionality of cellular organelles (Jarsch et al. 2016). Deformation of membranes is known to hinder organelle functionality and cause health repercussions to the cell and the individual. Mitochondria (an organelle) is impacted by abnormal membrane-binding and scaffolding of proteins.

Specific diseases had not been listed in the research, however, specific proteins and the roles they play in membrane alteration were listed. One specific protein complex that affects mitochondrial functionality is the F1F0-ATP synthase complex (Kondadi et al. 2019). The mitochondria consist of two membrane layers, an outer and an inner layer. The primary function of the mitochondria is to provide cells energy through oxidative phosphorylation (Kondadi et al. 2019). The chemical reactions needed for this pathway require a significant amount of surface area in the inner membrane. The surface area increases by the formation of invaginations (cristae membranes) (Kondadi et al. 2020). Dimerization of abundant F1F0-ATP synthase causes a scaffolding effect and can deform the cristae membrane. Once the cristae membrane is altered many problems can arise such as reduced ATP output, loss of Mitochondrial DNA (mtDNA), and potential rupturing of the cell (Kondadi et al. 2020). Loss of cristae is linked to Down syndrome, dementia, epilepsy, sclerosis, Parkinson’s disease, optic atrophy, diabetes, and cardiomyopathy (Kondadi et al. 2020). Further experimental research should be conducted to understand the proteins in membrane-bending pathways better. Connections between membrane-binding protein abnormalities and human diseases should also be studied. If connections are found research can focus on treatment options.

References

Jarsch, I. K., Daste, F., & Gallop, J. L. (2016). Membrane curvature in cell biology: An

integration of molecular mechanisms. The Journal of cell biology, 214(4), 375–387. https://doi.org/10.1083/jcb.201604003

Kondadi, A. K., Anand, R., Hänsch, S., Urbach, J., Zobel, T., Wolf, D. M., … & Reichert, A. S.

(2020). Cristae undergo continuous cycles of membrane remodeling in a MICOS?dependent manner. EMBO reports. 21(3), e49776.

Kondadi, A. K., Anand, R., & Reichert, A. S. (2019). Functional Interplay between Cristae

Biogenesis, Mitochondrial Dynamics and Mitochondrial DNA Integrity. International journal of molecular sciences, 20(17), 4311. https://doi.org/10.3390/ijms20174311

Prinz, W. A., & Hinshaw, J. E. (2009). Membrane-bending proteins. Critical reviews in

biochemistry and molecular biology, 44(5), 278-291.