Mitochondrial Genome Flashcards
Mitochondrial matrix houses proteins from ____, ____, ____, ____, ____, and some ____.
Inner membrane houses special ______ for ______, also has _____, and _________. (Permeable to ____ molecules, impermeable to ____ molecules)
Outer membrane is ____, which allows for _________. Also contains _____ for _____. (Permeable to ____ molecules, impermeable to ____ molecules)
Intermembrane space houses _____ proteins.
Mitochondrial matrix houses proteins from TCA, LIPID OXIDATION, UREA CYCLE, MITOCHONDRIAL PROTEIN SYNTHESIS MACHINERY, MITOCHONDRIAL DNA and some HEME ENZYMES.
Inner membrane houses special TRANSPORTERS for ENTRY INTO MATRIX, also has ETC, and ATP SYNTHESIZING COMPLEX. (Permeable to NEITHER SMALL OR LARGE molecules, impermeable to SMALL AND LARGE molecules)
Outer membrane is POROUS, which allows for ISO-pH WITH CYTOPLASM. Also contains SIGNALING RECEPTORS for APOPTOSIS. (Permeable to SMALL molecules, impermeable to LARGE molecules)
Intermembrane space houses APOPTOTIC proteins.
Nuclear encoded mitochondrial genes:
Mitochondrially encoded mt genes:
Mitochondrial DNA has _ introns
Nuclear: ribosomal proteins, replication, transcription, and translational regulatory proteins, DNA Pol Gamma, complex II, cytochome C, single-subunit POLRMT RNA polymerase
Mitochondrial: rRNAs, RNAs, some complex I, 1 complex III, some complex IV, some ATP synthase
ZERO INTRONS
D-loop is ______ and responsible for _____ and _____ control.
D-loop is NON-CODING and responsible for REPLICATION and TRANSCRIPTIONAL control.
The 2 additional proteins needed for mtDNA replication are: _____ helicase and _______
The 2 additional proteins needed for mtDNA replication are: TWINKLE helicase and mtSSB
MtDNA Transcription:
______ RNA polymerase is assisted by _____, ____, and / ______. _____ binds to ______ within promoter regions, giving rise to _____ transcripts that get processed by _____. MtRNAs have a _________.
MtDNA Transcription:
POLRMT RNA polymerase is assisted by TFAM (TRANSCRIPTION INITIATION FACTOR), AND TFB (TRANSCRIPTION ACTIVATOR), AND B1/B2 TFS. TFAM binds to TREs within promoter regions, giving rise to POLYCISTRONIC transcripts that get processed by RNASE-P. MtRNAs have a SHORT POLY-A TAIL.
MtDNA has a ___ mutation rate due to proximity to _____, and because it doesn’t have _____ and few ________. The ____ mutation rate makes comparisons of mtDNA useful for ________
MtDNA has a HIGH mutation rate due to proximity to OX-PHOS, and because it doesn’t have INTRONS and few REPAIR MECHANISMS. The HIGH mutation rate makes comparisons of mtDNA useful for FOLLOWING HUMAN LINEAGES.
There is a _____ amount of ATP required for cell survival in a given tissue. In a ______ cell, when the # of normal mtDNA _____________, the respiration and ATP synthesis of the cell may be insufficient and lead to _____.
There is a THRESHOLD amount of ATP required for cell survival in a given tissue. In a HETEROPLASMIC cell, when the # of normal mtDNA DROPS BELOW THRESHOLD, the respiration and ATP synthesis of the cell may be insufficient and lead to CELL DEATH.
Characteristic clinical features of defects in mtDNA: \_\_\_\_\_ inheritance pattern \_\_\_\_\_\_ in tissues among family members \_\_\_\_\_ onset \_\_\_\_\_\_ acidosis \_\_\_\_\_\_ \_\_\_\_\_\_ \_\_\_\_\_\_ in myofibers
Characteristic clinical features of defects in mtDNA:
MATERNAL inheritance pattern
VARIABILITY in tissues among family members
LATE onset
LACTIC acidosis
MASSIVE MITOCHONDRIAL PROLIFERATION in myofibers (RAGGED RED FIBERS)
Symptoms of mtDNA deletion diseases: \_\_\_\_\_ myopathy \_\_\_\_\_ acidosis \_\_\_\_\_ loss \_\_\_\_\_\_ Example: \_\_\_\_\_\_\_\_\_, characterized by \_\_\_\_\_ and \_\_\_\_\_
Symptoms of mtDNA deletion diseases: OCULAR myopathy LACTIC acidosis HEARING loss DEMENTIA Example: KEARNES-SAYRE, characterized by PROGRESSIVE MUSCLE WEAKNESS and RETINOPATHY
Example of mtDNA diseases caused by pt mutation:
________, characterized by ______ inheritance. Death of ____ nerve —-> sudden ______.
Pt mutation is ___—>___ in subunit _ of ______. Has other pt mutations in other complexes
Does not have ______
Example of mtDNA diseases caused by pt mutation:
LEBERS LHON, characterized by MATERNAL inheritance. Death of OPTIC nerve —-> sudden BLINDNESS.
Pt mutation is ARG—>HIS in subunit 4 of NADH DH. Has other pt mutations in other complexes
Does not have RED RAGGED FIBERS
Disease that usually arises from nuclear DNA mutations. Does not have ________
Leigh syndrome
Does not have RED RAGGED FIBERS
Warburg effect is when ____ cells switch from ________ to ______, which provides more _____ for growing _____ cells and _____ the likelihood of their destruction by __ _____.
The decrease in ____ ____ is promoted by defects in ______ and in _____.
Warburg effect is when CANCER cells switch from OX-PHOS to GLYCOLYSIS, which provides more SUBSTRATES for growing TUMOR cells and DECREASED the likelihood of their destruction by FREE RADICALS.
The decrease in OX PHOS is promoted by defects in POL GAMMA and in MTDNA.
Mitochondrial ____ and _____ allow for _____ of mutated mtDNA and mutated mitochondria.
Mitochondrial FUSION and FISSION allow for DISPOSAL of mutated mtDNA and mutated mitochondria.
If you have improperly folded ____ or ___ in mito, those issues can affect the machinery at all 4 complexes because they won’t be able to undergo _____.
If you have improperly folded tRNA or rRNA in mito, those issues can affect the machinery at all 4 complexes because they won’t be able to undergo TRANSLATION.
Distinctive features of mtDNA genetics
Very high mutation rate Maternal inheritance of mtDNA Bottleneck effect Random segregation of mt and mtDNA Threshold effect Changes with age
