User:Rtian96/sandbox

Topic: Mitochondrial Biogenesis

Outline

1) Expand on why mitochondria can self-replicate.

· The current introduction take 1-2 sentences to describe what mitochondria are and what they do.

· I would like to touch briefly on why mitochondria are able to self-replicate and perform this mechanism of mitochondrial biogenesis.

· It is rooted in the mitochondria being descended from endosymbiotic relationships between alpha-protobacteria and host cells, thus allowing them to have their own genome for self-replication.

· Include that fusion and fission reactions allow for constant mitochondrial reorganization.

2) Expand on how proteins encoded in the nucleus are able to reach and fold properly in the mitochondria · The current first body paragraph states that the majority of mitochondrial protein comes from the nuclear genome. I feel that it would be helpful to note that these nuclear proteins are translated in the cytosol but then transported to the mitochondria.

· I would like to describe how these precursor proteins pass through protein translocases on the mitochondria while in an unfolded state.

· I would like to note that proteins that are transported into the matrix have a particular pathway involving a signal at the N-terminus that will be cleaved. Apart from that, the majority of these mitochondrial protein precursors utilize targeting information within their protein sequence.

· Lastly, I would like to introduce some of the major membrane protein translocase complexes known to be involved in mitochondrial biogenesis as of now (TOM, TIM). These complexes provide gates for proteins with different targeting information.

3) Discuss regulation of mitochondrial biogenesis · While the article introduces PGC-1α as a master regulator/cofactor for mitochondrial genesis, multiple research studies have concluded that AMPK (AMP-activated kinase) is important for regulating mitochondrial biogenesis by activating PGC-1α

· I would also like to clarify that while there have been significant increases in mitochondria in tissues where PGC-1α is overexpressed, as the cofactor is thought to interact with the key transcription factors noted in the wiki article, mice with disrupted PGC-1α are still viable and show normal mitochondrial abundance. Therefore, PGC-1α is not required for normal development of mitochondria in mice, but under physiological stress, these mice exhibit reduced exercise tolerance

4) Aging · In order to maintain healthy mitochondria as we age, we need to constantly renew our mitochondria

· The capacity for mitochondrial biogenesis has been shown to decrease with age

· Changes in the expression levels of proteins involved in fusion and fission reactions can cause dysfunctional mitochondria that comes with age or disease

· Direct correlation between decreasing telomerase reverse transcriptase (TERT) that comes with aging with lower PGC- 1α expression and suppressed mitochondrial biogenesis

5) Create and add image for page

Research:

1. Bo, Hai, Yong Zhang, and Li Li Ji. "Redefining the Role of Mitochondria in Exercise: A Dynamic Remodeling." Annals of the New

York Academy of Sciences 1201.1 (2010): 121-28. Web.

2. Gurd, B. J., Y. Yoshida, J. T. Mcfarlan, G. P. Holloway, C. D. Moyes, G. J. F. Heigenhauser, L. Spriet, and A. Bonen. "Nuclear

SIRT1 Activity, but Not Protein Content, Regulates Mitochondrial Biogenesis in Rat and Human Skeletal Muscle." AJP:

Regulatory, Integrative and Comparative Physiology 301.1 (2011): n. pag. Web.

3. Jornayvaz, Francois R., and Gerald I. Shulman. "Regulation of Mitochondrial Biogenesis." Essays In Biochemistry 47 (2010):

69-84. Web.

4. Scarpulla, Richard C. "Metabolic Control of Mitochondrial Biogenesis through the PGC-1 Family Regulatory Network." 

Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research 1813.7 (2011): 1269-278. Web.

5. Ventura-Clapier, R., A. Garnier, and V. Veksler. "Transcriptional Control of Mitochondrial Biogenesis: The Central Role of PGC-

1α." Cardiovascular Research 79.2 (2008): 208-17. Web.

6. Wenz, Tina. "Mitochondria and PGC-1α in Aging and Age-Associated Diseases." Journal of Aging Research 2011 (2011): 1-12.

Web.