This document discusses the role of mitochondria in cancer. It covers several topics: 1) Mitochondrial DNA mutations can be inherited from the mother and contribute to cancer development. 2) Mitochondria are integrated into various cellular processes like catabolism, signaling, and anabolism that influence cancer. 3) Studies have found mutations in the mitochondrial genome in over 2000 human cancers across 30 tumor types. 4) Defective mitochondria accumulate in rare benign tumors called oncocytomas due to pathogenic mitochondrial DNA mutations. 5) Different subtypes of cancers exhibit different mitochondrial phenotypes depending on their mutation burden and metabolic needs.

1. RIMSHA FAROOQ
BBS 153009
Presented to : Dr. Shaukat Iqbal Malik

2. Mitochondrial DNA and Cancer

3. Introduction
Mitochondrial integration
Mitochondrial genome
Mitochondrial quality
Defective mitochondria
Subtypes of tumors
Tumors accumulate respiration
CONTENTS

4. INTRODUCTION
• Maternal inheritance of pathogenic mutant
mitochondrial genomes
• Warburg effect

5. MITOCHONDRIAL INTEGRATION
Integration in
catabolism
Integration in
during signaling
Integration in
anabolism

6. THE MITOCHONDRIAL GENOME IN
CANCER
Status and role of mutation in
mitochondrial DNA
Mitochondrial genome in over 2000 human cancers across
more than 30 tumor types
Somatic substitutions with strong
replicative strand bias

7. MITOCHONDRIAL QUALITY
CONTROL IN CANCER
Depolarization
of mt
membrane
Activation of
PINK 1
Recruitment of
E3 ligase
PARKIN
ubiquitinylation
of mt proteins
Recruitment of
autophagy
Mitophagy in
cancer

8. ONCOCYTOMAS ACCUMULATE
DEFECTIVE MITOCHONDRIA
Oncocytomas are
rare, benign tumors
of most epithelia
characterized by the
vast accumulation of
defective
mitochondria due to
pathogenic mtDNA
mutations

9. DIFFERENT SUBTYPES OF
MITOCHONDRIA RICH TUMORS
• Accumulation of
mutant Mitochondria
• Syndromes that
develop spontaneous
renal tumors

10. MALIGNANT TUMORS ACCUMULATE
RESPIRATION FUNCTIONAL
MITOCHONDRIA
• Higher rates of
respiration
• Mitochondrial defects
and intact
mitochondrial
function
• Repressed mitophagy

11. MUTATIONS IN TCA CYCLE
ENZYMES PROMOTE CANCER
• Isocitrate dehydrogenase
(IDH) 2, succinate
dehydrogenase (SDH)×
(SDHA-D and SDHAF2),
and fumarate hydratase
(FH) are found in human
cancers

12. TARGETING OF MITOCHONDRIAL
METABOLISM FOR CANCER
THERAPY
• Sensitivity to low
glucose and OXPHOS
• Inhibiting autophagy
and mitophagy can
interfere with
mitochondrial
metabolism