American Society of Hematology

Figure 5

$Figure 5. LCL-461 accumulates in mitochondria to induce LC3B-dependent lethal mitophagy regardless of FLT3 mutation status. (A) Chemical structure of LCL-461 or C18-pyridinium ceramide. (B) MS detection of LCL-461 in mitochondrial, cytosolic, and nuclear fractions in vehicle and LCL-461–treated MV4-11 or normal human bone marrow cells. (C) Percentage of viability measured using MTT assay in MV4-11, MV4-11–resistant, sh-LC3B, and sh-Drp1 cells in response to LCL-461. (D) Percentage of viability measured using the MTT assay of AML cell lines with different FLT3 mutations in response to LCL-461. (E) Western blot showing LC3B in LCL-461–treated cells transfected with scr or Drp1 siRNA. (F) EM visualization of mitophagosomes induced by LCL-461 treatment in MV4-11 cells treated with 5 μM LCL-461. White arrows indicate autophagosomes and black arrows indicate mitochondria. Values indicate mean ± SD of n = 3. *P value of <.05 using the 2-sided Student t test.$

LCL-461 accumulates in mitochondria to induce LC3B-dependent lethal mitophagy regardless of FLT3 mutation status. (A) Chemical structure of LCL-461 or C₁₈-pyridinium ceramide. (B) MS detection of LCL-461 in mitochondrial, cytosolic, and nuclear fractions in vehicle and LCL-461–treated MV4-11 or normal human bone marrow cells. (C) Percentage of viability measured using MTT assay in MV4-11, MV4-11–resistant, sh-LC3B, and sh-Drp1 cells in response to LCL-461. (D) Percentage of viability measured using the MTT assay of AML cell lines with different FLT3 mutations in response to LCL-461. (E) Western blot showing LC3B in LCL-461–treated cells transfected with scr or Drp1 siRNA. (F) EM visualization of mitophagosomes induced by LCL-461 treatment in MV4-11 cells treated with 5 μM LCL-461. White arrows indicate autophagosomes and black arrows indicate mitochondria. Values indicate mean ± SD of n = 3. *P value of <.05 using the 2-sided Student t test.

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