0792 Group 8

Roca, Alexandra Margarette

Rentiquiano, Desiree

Ruiz, Chrinssie Vivien

Ruiz, Kimberly

Santos, Candice
1. Illustrate and discuss the effect of ischemia on mitochondrial function
- Mitochondria are one of the enzymatic sources of reactive oxygen species (ROS) and could also
be a major target for ROS. Cardiolipin, a phospholipid of unusual structure localized almost
exclusively within the mitochondrial membrane is particularly rich in unsaturated fatty acids.
Thus, mitochondrial cardiolipin molecules are a possible and earl target of ROS attack, either
because of their high content of unsat. FA or because of their location in the inner mitochondrial
membrane near to the site of ROS production, mainly at the level of complexes I and III of the
respiratory chain. Furthermore, ROS can damage various cellular components such as proteins,
lipids, and DNAs. Mitochondrial injury is reflected by mitochondrial DNA (mtDNA) damage as
well as by a decline in the mtRNA transcripts, protein synthesis, and mitochondrial function.
mtDNA is more susceptible to oxidative attack than nuclear DNA, possible because of its
proximity to the respiratory chain in the mitochondrial inner membrane, the lack of histone-like
proteins, and its poor repair activity against damage. mtDNA mutations may prevent its
repplication or expression. Therefore, mitochondrial ROS may resut in the progressive
destruction of the mtDNA and such mtDNA damage can lead to a decline of mtRNA
transcription and a loss of function. Recent in vitro studies have clearly shown the ROS mediate
mtDNA damage, alterations of gene expression, and mitochondrial dysfunction in cultured
vascular endothelial and smooth muscle cells. That being said, mitochondria plays a pivotal role
in the maintenance of cardiac function through energy production and the regulation of apoptosis
and ROS, and mitochondrial dysfunction might lead to myocardial dysfunction, progression of
LV remodeling and worsening heart failure. Mitochondria contain several copies of circular
mitochondrial DNA molecules, and this mitochondrial copy number (MCN) is important for
preserving mitochondrial function. MCN might reflect the process of LV remodeling. In previous
clinical studies, decrease in mitochondrial DNA content was correlated in end stage heart failure.
Under MCN, we have Leukocyte MCN which reflects m now mitochondrial dysfunction during
acute ischemia and reperfusion, might be a useful biomarker to identify acute myocardial
infarction patients at high risk of developing heart failure.
2. Illustrate and describe the pathophysiology of a clinical condition whose pathology is due to
genetic derangements.

- Genetic abnormalities may result in a defect as severe as the congenital malformations associated
with Down syndrome, caused by a chromosomal anomaly, or as subtle as the decreased life span
of red blood cells caused by a single amino acids substitution in hemoglobin in sickle cell anemia.
Genetic defects may cause cell injury because of deficiency of functional proteins, such as
enzyme defects in inborn errors of metabolism or accumulation of damaged DNA or misfolded
proteins, both of which trigger cell death when they are beyond repair. Variations in the genetic
makeup can also influence the susceptibility of cells to injury by chemicals and other
environmental results.
References:

Valenti, D & Vacca, RA., et.al. (2014). Mitochondria dysfunction as a central actor in intellectual
disability-related disease: an overview of own syndrome, autism, Fragile X and Rett syndrome. Newyork:
Elsevier, Ltd. Retrieved from https://www.sciencedirect.com/science/article/pii/S0149763414000256.

Cup-hill, R. &Zheng, C., et.al. (2018). Red blood cell metabolism in down syndrome: hints on metabolic
derangements in aging. USA: American society of Hematology.

Retrieved from www.sciencedirect.com. (2018). Elsevier.

Ide, T. & Tsutsui H., et.al. (2001). Mitochondrial DNA damage and dysfunction associated with oxidative
stress in failing hearts after myocardial infarction. Japan: Circ Res. 88(5):529-35. Retrieved from:
htpps://www.ncbi.nlm.nih.gov.

Tsuburaya, R. (2017). Mitochondrial dysfunction and left ventricular structural remodeling after acute
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Kumar, V. & Hogge, A., et.al. (2014).Robbins and Cotran Pathologic basis of disease.(9 th Ed.). USA:
Elsevier