TY - JOUR
T1 - Fusion or fission: The destiny of mitochondria in traumatic brain injury of different severities
AU - Di Pietro, Valentina
AU - Lazzarino, Giacomo
AU - Amorini, Angela Maria
AU - Signoretti, Stefano
AU - Hill, Lisa J.
AU - Porto, Edoardo
AU - Tavazzi, Barbara
AU - Lazzarino, Giuseppe
AU - Belli, Antonio
PY - 2017
Y1 - 2017
N2 - Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.
AB - Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.
KW - Cancer Research
KW - Cell Biology
KW - Cellular and Molecular Neuroscience
KW - Immunology
KW - Cancer Research
KW - Cell Biology
KW - Cellular and Molecular Neuroscience
KW - Immunology
UR - http://hdl.handle.net/10807/120483
UR - http://www.nature.com/srep/index.html
U2 - 10.1038/s41598-017-09587-2
DO - 10.1038/s41598-017-09587-2
M3 - Article
SN - 2045-2322
VL - 2017
SP - 9189
EP - 9198
JO - Scientific Reports
JF - Scientific Reports
ER -