Related Experiment Video

Updated: Jul 14, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

18.2K

Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury

Wenjia Xie1, Qingyun He1, Yan Zhang1

  • 1Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Cell Death & Disease
|October 10, 2023
PubMed

Insights

Pyruvate kinase M2 (PKM2) drives mitochondrial fragmentation in acute kidney injury (AKI). Inhibiting PKM2

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Acute kidney injury (AKI) involves mitochondrial fragmentation in renal tubular cells, leading to cell death.
  • Pyruvate kinase M2 (PKM2) regulates glycolysis and cell survival, but its role in AKI is unclear.

Purpose of the Study:

  • To elucidate the mechanism of PKM2 in regulating cell survival during AKI.
  • To investigate PKM2's role in mitochondrial fragmentation and cell death in AKI.

Main Methods:

  • Studied PKM2 phosphorylation, dimerization, and mitochondrial translocation in response to AKI-inducing agents (staurosporine, cisplatin).
  • Investigated the interaction of mitochondrial PKM2 with myosin heavy chain 9 (MYH9) and dynamin-related protein 1 (DRP1).
  • Assessed the effects of PKM2 loss/activity modulation and MYH9 inhibition on mitochondrial fragmentation and cell death in vitro and in vivo.

Main Results:

  • PKM2 phosphorylation induced its dimerization and mitochondrial translocation.
  • Mitochondrial PKM2, via MYH9, promotes DRP1-mediated mitochondrial fragmentation.
  • PKM2 modulation limited fragmentation and cell death (apoptosis, necroptosis, ferroptosis), alleviating renal injury.
  • Inhibiting MYH9 reversed staurosporine/cisplatin-induced mitochondrial fragmentation and cell death.

Conclusions:

  • PKM2 translocation into mitochondria contributes to AKI pathogenesis by promoting mitochondrial fragmentation.
  • Targeting PKM2 abundance and activity to prevent mitochondrial translocation may preserve mitochondrial integrity.
  • This offers a potential therapeutic strategy for AKI treatment.

More Related Videos

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish13:25

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Published on: May 15, 2021

5.8K
Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research03:13

Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research

Published on: November 3, 2023

2.3K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.3K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.6K
Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
11
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
20