Abstract
Aggressive prostate cancer is characterized by altered lipid metabolism and
metabolic stress. At a subcellular level these changes are localized to the
endoplasmic reticulum (ER) and mitochondria. Traditionally the function of these
organelles has been studied separately. A growing body of evidence shows that
the interaction between mitochondria and ER at specialized membrane contact
sites play a key role in regulating fundamental cellular processes such as lipid
synthesis, mitochondrial metabolism, calcium signaling, apoptosis and oxidative
stress. In this study we have undertaken the first high resolution imaging study of
prostate tissue to evaluate changes in mitochondrial ER-associated membranes
(MAMs). We have analyzed the number and size of MAMs in human patient
samples with varying Gleason grade groups using transmission electron
microscopy. Quantification of the number of mitochondria in close spatial
proximity (0–25 nm) to the ER in intermediate grade cancer compared to normal
tissue, showed a prominent increase in tight membrane contacts. In control cells
15% of mitochondria associated closely with the ER compared to 75% in the
transformed cells. Furthermore, the size of the contact sites in transformed cells
was larger compared to control and covered 15% of the mitochondria perimeter,
suggesting a more efficient lipid and calcium transfer at these contact sites in
transformed prostate epithelial cells. Based on these findings we believe that
organelle proximity and contact sites represent pathological features of prostate
cancer, which may correlate with metabolic reprogramming occurring during
prostate cancer progression. Our current efforts focus on identifying the protein
complexes that mediate the associations between organelles and evaluating
whether the occurrence of MAMs impacts on treatment responses and the
development of treatment resistance.
Original language | English |
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Title of host publication | Oncology Abstracts |
Publisher | BioScientifica Ltd. |
Number of pages | 1 |
Volume | 1 |
ISBN (Electronic) | 2631-4657 |
DOIs | |
Publication status | Published - 09 Dec 2019 |