Autophagy has emerged as a novel mechanism for tumor suppression. It has been postulated that defective autophagy leads to the accumulation of damaged proteins or organelles, resulting in genome instability and cancer. We have observed that a Bcl-2 family member, Nix, is required for selective autophagy of mitochondria that have lost mitochondrial membrane potential. Dysfunctional mitochondria can produce reactive oxygen species to cause DNA damage. However, it is unclear whether selective mitochondrial autophagy is important for preventing damages to mitochondrial and nuclear DNA. We hypothesize that selective mitochondrial autophagy plays a critical role in mitochondrial quality control. Accumulation of dysfunctional mitochondria due to defective autophagy may cause increases in DNA damage, leading to genome instability. We propose 1) to determine the role for mitochondrial autophagy in protecting genome stability;2) to characterize the molecular mechanisms of specific recognition of dysfunctional mitochondria by autophagosomes. This study may help to reveal molecular events of autophagy as novel biomarkers for mitochondrial quality control in the protection against genome instability and cancer.

Public Health Relevance

Narrative This study seeks to identify the molecular events in autophagy as novel biomarkers in mitochondrial quality control and the prevention of genome instability.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA152076-02
Application #
8089250
Study Section
Cancer Molecular Pathobiology Study Section (CAMP)
Program Officer
Salnikow, Konstantin
Project Start
2010-07-01
Project End
2013-12-31
Budget Start
2011-07-01
Budget End
2013-12-31
Support Year
2
Fiscal Year
2011
Total Cost
$198,106
Indirect Cost
Name
Baylor College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030