Bruno B. Queliconi

Universidade de São Paulo

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Alicia J. Kowaltowski

Universidade de São Paulo

Daria Mochly‐Rosen

Stanford University

Julio Cesar Batista Ferreira

Universidade de São Paulo

Juliane C. Campos

Universidade de São Paulo

Luiz R. G. Bechara

Universidade de São Paulo

Noriyuki Matsuda

University of Toyama

Koji Yamano

Tokyo Medical and Dental University

Paulo Magno Martins Dourado

Hospital do Coração

Nicolai P. Ostberg

Stanford University

Bereketeab Haileselassie

Stanford Medicine

Cooperative Institutions

Stanford University

Universidade de São Paulo

University of California, San Francisco

The University of Tokyo

Tokyo Metropolitan Institute of Medical Science

Gladstone Institutes

Palo Alto University

Japan Science and Technology Agency

National Institutes of Health

Instituto de Botânica

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Redox regulation of the mitochondrial KATP channel in cardioprotection

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2010)

Bruno B. Queliconi Andrew P. Wojtovich Sergiy M. Nadtochiy Alicia J. Kowaltowski Paul S. Brookes

Cardioprotection

Nitroxyl

ATP-sensitive potassium channel

Adenosine triphosphate

10.1016/j.bbamcr.2010.11.005

Cite

Citations (94)

Mitochondrial Reactive Oxygen Species in Myocardial Pre- and Postconditioning

Humana Press eBooks (2010)

Ariel R. Cardoso Bruno B. Queliconi Alicia J. Kowaltowski

Myocardial ischemia followed by reperfusion is a well established condition of medical importance in which reactive oxygen species (ROS) are determinant for the pathological outcome. Indeed, oxidative damage during reperfusion is causative of many of the complications found after ischemia. ROS leading to postischemic myocardial damage come from many sources, including mitochondria, NADPH oxidase, xanthine oxidase, and infiltrated phagocytes [1]. ROS also can act as signaling molecules in the cardiovascular system, including protecting the heart against myocardial ischemic damage, secondarily to ischemic pre- and postconditioning. In this case, there is ample evidence that the source of signaling ROS is mitochondrial [2–7]. This chapter will briefly review aspects of mitochondrial ROS signaling relevant to myocardial ischemic protection by pre- and postconditioning.

Mitochondrial ROS

10.1007/978-1-60761-600-9_5

Cite

Citations (1)

Organ-specific fuel rewiring in acute and chronic hypoxia redistributes glucose and fatty acid metabolism

Cell Metabolism (2023)

Ayush Midha Yuyin Zhou Bruno B. Queliconi Alec M. Barrios Augustinus G. Haribowo

Hypoxia

Carbohydrate Metabolism

Fatty Acid Metabolism

10.1016/j.cmet.2023.02.007

Cite

Citations (27)

Aerobic exercise training improves cardiac mitochondrial function and redox balance status in rats

Resumos (2011)

Juliane C. Campos Bruno B. Queliconi Maria Kátia Gomes Paulo Magno Martins Dourado Patrı́cia C. Brum

Aerobic Exercise

Source

Cite

Citations (0)

Abstract 344: Basis for Bicarbonate Damage in Myocardial Ischemia/Reperfusion Injury

Circulation Research (2014)

Bruno B. Queliconi Fernanda Marques da Cunha Roberta A. Gottlieb Alicia J. Kowaltowski

In the clinical setting, bicarbonate is often used to correct acidosis arising from accumulated CO2/HCO3- during ischemia. We observed that HL-1 cardiomyocytes exposed to increased [CO2/HCO3-] had more cell death after hypoxia/reoxygenation (H/R) and Langendorff-perfused rat hearts had larger infarcts after ischemia/reperfusion (I/R). In addition to buffering pH, the CO2/HCO3- pair possess an underappreciated redox activity that may contribute to injury. In order to study the effects of high CO2/HCO3- during ischemic injury independent of pH, we clamped pH using HEPES and used the mouse cardiomyocyte HL-1 cell line and isolated perfused rat hearts. HL-1 cells exposed to 10% CO2/HCO3- had no damage under basal conditions but developed exaggerated protein carbonylation and cell death after H/R. In Langendorff-perfused rat hearts, 10% CO2 was well tolerated during baseline conditions but resulted in increased protein carbonylation, cell death and larger infarcts after I/R. We hypothesized that the increased oxidative damage to proteins could be due to mitochondrial dysfunction with greater ROS production, diminished proteasomal degradation of oxidized proteins, or impaired autophagic clearance of damaged mitochondria and oxidized protein aggregates. There was no differential effect of CO2 on mitochondrial morphology or proteasomal activity in HL-1 cells. In mitochondria isolated from perfused hearts subjected to I/R under low and high CO2 conditions, there was no difference in ROS production or oxidized protein content, suggesting mitochondrial damage was not affected by CO2 level. Examination of autophagy in HL-1 cells exposed to high CO2 during H/R revealed higher LC3-II and lower p62 content. In hearts, changes in LC3-II were inconsistent; however, we detected less p62 protein, less mitochondria-associated Beclin1, and significantly more LC3 mRNA in hearts exposed to 10% CO2 during I/R. Taken together, these findings suggest that 10% CO2 affects autophagy, which could explain the accumulation of oxidatively damaged proteins. These findings point to a protective role for autophagic clearance of oxidized protein aggregates during I/R injury that may be adversely impacted by bicarbonate therapy.

Protein Carbonylation

Bicarbonate

10.1161/res.115.suppl_1.344

Cite

Citations (0)

Unfolding is the driving force for mitochondrial import and degradation of the Parkinson's disease-related protein DJ-1

Journal of Cell Science (2021)

Bruno B. Queliconi Waka Kojima Mayumi Kimura Kenichiro Imai Chisato Udagawa

Diverse genes associated with familial Parkinson's disease (familial Parkinsonism) have been implicated in mitochondrial quality control. One such gene, PARK7 encodes the protein DJ-1, pathogenic mutations of which trigger its translocation from the cytosol to the mitochondrial matrix. The translocation of steady-state cytosolic proteins like DJ-1 to the mitochondrial matrix upon missense mutations is rare, and the underlying mechanism remains to be elucidated. Here, we show that the protein unfolding associated with various DJ-1 mutations drives its import into the mitochondrial matrix. Increasing the structural stability of these DJ-1 mutants restores cytosolic localization. Mechanistically, we show that a reduction in the structural stability of DJ-1 exposes a cryptic N-terminal mitochondrial-targeting signal (MTS), including Leu10, which promotes DJ-1 import into the mitochondrial matrix for subsequent degradation. Our work describes a novel cellular mechanism for targeting a destabilized cytosolic protein to the mitochondria for degradation.

Mitochondrial matrix

DNAJA3

10.1242/jcs.258653

Cite

Citations (5)

Bicarbonate Increases Ischemia-Reperfusion Damage by Inhibiting Mitophagy

PLoS ONE (2016)

Bruno B. Queliconi Alicia J. Kowaltowski Roberta A. Gottlieb

During an ischemic event, bicarbonate and CO2 concentration increase as a consequence of O2 consumption and lack of blood flow. This event is important as bicarbonate/CO2 is determinant for several redox and enzymatic reactions, in addition to pH regulation. Until now, most work done on the role of bicarbonate in ischemia-reperfusion injury focused on pH changes; although reperfusion solutions have a fixed pH, cardiac resuscitation protocols commonly employ bicarbonate to correct the profound acidosis associated with respiratory arrest. However, we previously showed that bicarbonate can increase tissue damage and protein oxidative damage independent of pH. Here we show the molecular basis of bicarbonate-induced reperfusion damage: the presence of bicarbonate selectively impairs mitophagy, with no detectable effect on autophagy, proteasome activity, reactive oxygen species production or protein oxidation. We also show that inhibition of autophagy reproduces the effects of bicarbonate in reperfusion injury, providing additional evidence in support of this mechanism. This phenomenon is especially important because bicarbonate is widely used in resuscitation protocols after cardiac arrest, and while effective as a buffer, may also contribute to myocardial injury.

Bicarbonate

10.1371/journal.pone.0167678

Cite

Citations (25)

Evaluation of cryptic mitochondrial targeting signal of DJ-1

The Japanese Biochemical Society/The Molecular Biology Society of Japan (2017)

Waka Kojima Koji Yamano Mayumi Kimura Bruno B. Queliconi Keiji Tanaka

SIGNAL (programming language)

Source

Cite

Citations (0)

Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

PLoS ONE (2012)

Juliane C. Campos Bruno B. Queliconi Paulo Magno Martins Dourado Telma F. Cunha Vanessa O. Zambelli

Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H2O2 release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H2O2 resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca2+-induced permeability transition and reduced H2O2 release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therapy.

10.1371/journal.pone.0052764

Cite

Citations (84)

Cardiac Troponin I Directly Binds and Inhibits Mitochondrial ATP Synthase: a Noncanonical Role in the Post-Ischemic Heart

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Aly Elezaby Amanda Lin Vijith Vijayan Suman Pokhrel Luiz R. G. Bechara

Abstract Cardiac troponin I (cTnI) is a sarcomeric protein critical to myocyte contraction. Unexpectedly, we found that some cTnI localized to the mitochondrial matrix in the heart, inhibited mitochondrial functions when stably expressed in non-cardiac cells and increased opening of the mitochondrial permeability transition pore under oxidative stress. Direct, specific, and saturable binding of cTnI to ATP synthase was demonstrated in vitro , using immune-captured ATP synthase, and in cells using proximity ligation assay. cTnI binding doubled F 1 F 0 ATPase activity, whereas skeletal troponin I and several human mutant cTnI variants associated with familial hypertrophic cardiomyopathy did not. A rationally-designed ten amino acid peptide, P888, inhibited cTnI binding to ATP synthase, inhibited cTnI-induced increase in ATPase activity in vitro , and reduced cardiac injury following transient ischemia in vivo . We therefore suggest that mitochondria-associated cTnI may inhibit cardiac ATP synthase under basal conditions; pharmacological agents that release this inactivating effect of cTnI and thus preventing ATP hydrolysis during cardiac ischemia may increase the reservoir of functional mitochondria to reduce cardiac injury. Significance Statement Cardiac troponin I (cTnI) is a key sarcomeric protein involved in the regulation of myocardial contractility. We found that some cTnI is present in the mitochondrial matrix where it binds to ATP synthase, disrupting mitochondrial function; inhibition of the cTnI-ATP synthase interaction with a selective peptide inhibitor reduces cardiac dysfunction following ischemia and reperfusion injury. Several pathogenic cTnI mutations associated with hypertrophic cardiomyopathy do not affect ATP synthase activity, suggesting a potential mechanism that contributes to the diverse pathologies associated with these mutations.

Inhibitor protein

10.1101/2023.02.03.526715

Cite

Citations (2)